Immune-based therapies in diffuse large B-cell lymphoma

References

• Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017 Oct 19;130(16):1800–1808.
   PubMed Web of Science ®Google Scholar
• Morin RD, Arthur SE, Hodson DJ. Molecular profiling in diffuse large B-cell lymphoma: why so many types of subtypes? Br J Haematol. 2022 Feb;196(4):814–829. doi: 10.1111/bjh.17811
   PubMed Web of Science ®Google Scholar
• Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000 Feb 3;403(6769):503–511.
   PubMed Web of Science ®Google Scholar
• Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235–242. doi: 10.1056/NEJMoa011795
   PubMed Web of Science ®Google Scholar
• Philip T, Guglielmi C, Hagenbeek A, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540–1545.
   PubMed Web of Science ®Google Scholar
• Westin J, Sehn LH. CAR T cells as a second-line therapy for large B-cell lymphoma: a paradigm shift? Blood. 2022;139(18):2737–2746. doi: 10.1182/blood.2022015789
   PubMed Web of Science ®Google Scholar
• Kochenderfer JN, Dudley ME, Kassim SH, et al. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol. 2015 Feb 20;33(6):540–549.
   PubMed Web of Science ®Google Scholar
• Kochenderfer JN, Dudley ME, Carpenter RO, et al. Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Blood. 2013 Dec 12;122(25):4129–4139.
   PubMed Web of Science ®Google Scholar
• Schuster SJ, Svoboda J, Dwivedy Nasta S, et al. Sustained remissions following chimeric antigen receptor modified T cells directed against CD19 (CTL019) in patients with relapsed or refractory CD19+ lymphomas. Blood. 2015;126(23):183–183. doi: 10.1182/blood.V126.23.183.183
   Web of Science ®Google Scholar
• Kochenderfer JN, Dudley ME, Feldman SA, et al. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood. 2012 Mar 22;119(12):2709–2720.
   PubMed Web of Science ®Google Scholar
• Spiegel JY, Dahiya S, Jain MD, et al. Outcomes of patients with large B-cell lymphoma progressing after axicabtagene ciloleucel therapy. Blood. 2021 Apr 1;137(13):1832–1835.
   PubMed Web of Science ®Google Scholar
• Chong EA, Ruella M, Schuster SJ. Five-year outcomes for refractory B-Cell lymphomas with CAR T-Cell therapy. N Engl J Med. 2021;384(7):673–674. doi: 10.1056/NEJMc2030164
   PubMed Web of Science ®Google Scholar
• Chow VA, Gopal AK, Maloney DG, et al. Outcomes of patients with large B-cell lymphomas and progressive disease following CD19-specific CAR T-cell therapy. Am J Hematol. 2019;94(8):E209–E213. doi: 10.1002/ajh.25505
   PubMed Web of Science ®Google Scholar
• Salles G, Duell J, Gonzalez Barca E, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020 Jul;21(7):978–988.
   PubMed Web of Science ®Google Scholar
• Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020 Sep 19;396(10254):839–852.
   PubMed Web of Science ®Google Scholar
• Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022 Jun 18;399(10343):2294–2308.
   PubMed Web of Science ®Google Scholar
• Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-Cell lymphoma. N Engl J Med. 2022 Feb 17;386(7):640–654.
   PubMed Web of Science ®Google Scholar
• Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-Cell therapy in refractory large B-Cell lymphoma. N Engl J Med. 2017 dec 28;377(26):2531–2544. doi: 10.1056/NEJMoa1707447
   PubMed Web of Science ®Google Scholar
• Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab vedotin in previously untreated diffuse large B-Cell lymphoma. N Engl J Med. 2022 Jan 27;386(4):351–363. doi: 10.1056/NEJMoa2115304
   PubMed Web of Science ®Google Scholar
• Pedersen IM, Buhl AM, Klausen P, et al. The chimeric anti-CD20 antibody rituximab induces apoptosis in B-cell chronic lymphocytic leukemia cells through a p38 mitogen activated protein-kinase-dependent mechanism. Blood. 2002 Feb 15;99(4):1314–1319.
   PubMed Web of Science ®Google Scholar
• Mathas S, Rickers A, Bommert K, et al. Anti-CD20- and B-cell receptor-mediated apoptosis: evidence for shared intracellular signaling pathways. Cancer Res. 2000 Dec 15;60(24):7170–7176.
   PubMed Web of Science ®Google Scholar
• Jazirehi AR, Huerta-Yepez S, Cheng G, et al. Rituximab (chimeric anti-CD20 monoclonal antibody) inhibits the constitutive nuclear factor-{kappa}B signaling pathway in non-Hodgkin’s lymphoma B-cell lines: role in sensitization to chemotherapeutic drug-induced apoptosis. Cancer Res. 2005 Jan 01;65(1):264–276.
   PubMed Web of Science ®Google Scholar
• Peyrade F, Bologna S, Delwail V, et al. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group. Lancet Haematol. 2017 Jan;4(1):e46–e55.
   PubMed Web of Science ®Google Scholar
• Flinn IW, Erter J, Daniel DB, et al. Phase II study of bendamustine and ofatumumab in elderly patients with newly diagnosed diffuse large B-Cell lymphoma who are poor candidates for R-CHOP chemotherapy. Oncology. 2019 Aug;24(8):1035–e623.
   Google Scholar
• Bonavida B. Postulated mechanisms of resistance of B-cell non-Hodgkin lymphoma to rituximab treatment regimens: strategies to overcome resistance. Semin Oncol. 2014 Oct;41(5):667–677. doi: 10.1053/j.seminoncol.2014.08.006
   PubMed Web of Science ®Google Scholar
• Shimizu R, Kikuchi J, Wada T, et al. HDAC inhibitors augment cytotoxic activity of rituximab by upregulating CD20 expression on lymphoma cells. Leukemia. 2010 Oct;24(10):1760–1768.
   PubMed Web of Science ®Google Scholar
• de Vos S, Goy A, Dakhil SR, et al. Multicenter randomized phase II study of weekly or twice-weekly bortezomib plus rituximab in patients with relapsed or refractory follicular or marginal-zone B-cell lymphoma. J Clin Oncol. 2009 Oct 20;27(30):5023–5030.
   PubMed Web of Science ®Google Scholar
• Gu JJ, Hernandez-Ilizaliturri FJ, Kaufman GP, et al. The novel proteasome inhibitor carfilzomib induces cell cycle arrest, apoptosis and potentiates the anti-tumour activity of chemotherapy in rituximab-resistant lymphoma. Br J Haematol. 2013 Sep;162(5):657–669.
   PubMed Web of Science ®Google Scholar
• Wanner K, Hipp S, Oelsner M, et al. Mammalian target of rapamycin inhibition induces cell cycle arrest in diffuse large B cell lymphoma (DLBCL) cells and sensitises DLBCL cells to rituximab. Br J Haematol. 2006 Sep;134(5):475–484.
   PubMed Web of Science ®Google Scholar
• Pro B, Leber B, Smith M, et al. Phase II multicenter study of oblimersen sodium, a Bcl-2 antisense oligonucleotide, in combination with rituximab in patients with recurrent B-cell non-Hodgkin lymphoma. Br J Haematol. 2008 Nov;143(3):355–360.
   PubMed Web of Science ®Google Scholar
• Ahmadi T, Chong EA, Gordon A, et al. Combined lenalidomide, low-dose dexamethasone, and rituximab achieves durable responses in rituximab-resistant indolent and mantle cell lymphomas. Cancer. 2014 Jan 15;120(2):222–228.
   PubMed Web of Science ®Google Scholar
• Westin J, Davis RE, Feng L, et al. Smart start: rituximab, lenalidomide, and ibrutinib in patients with newly diagnosed large B-Cell lymphoma. J Clin Oncol. 2023 Feb 1;41(4):745–755.
   PubMed Web of Science ®Google Scholar
• Wu L, Adams M, Carter T, et al. Lenalidomide enhances natural killer cell and monocyte-mediated antibody-dependent cellular cytotoxicity of rituximab-treated CD20+ tumor cells. Clin Cancer Res. 2008 Jul 15;14(14):4650–4657.
   PubMed Web of Science ®Google Scholar
• Nakamura K, Casey M, Oey H, et al. Targeting an adenosine-mediated “don’t eat me signal” augments anti-lymphoma immunity by anti-CD20 monoclonal antibody. Leukemia. 2020 Oct;34(10):2708–2721.
   PubMed Web of Science ®Google Scholar
• Mougiakakos D, Voelkl S, Bach C, et al. Mechanistic characterization of tafasitamab-mediated antibody-dependent cellular phagocytosis alone or in combination with lenalidomide. Blood. 2019 2019 nov 13;134(Supplement_1):4064. doi: 10.1182/blood-2019-124886.
   Google Scholar
• Tomita A. Genetic and epigenetic modulation of CD20 expression in b-cell malignancies: molecular mechanisms and significance to rituximab resistance. J Clin Exp Hematop. 2016;56(2):89–99. doi: 10.3960/jslrt.56.89
   PubMedGoogle Scholar
• Horton HM, Bernett MJ, Pong E, et al. Potent in vitro and in vivo activity of an Fc-engineered anti-CD19 monoclonal antibody against lymphoma and leukemia. Cancer Res. 2008 Oct 1;68(19):8049–8057.
   PubMed Web of Science ®Google Scholar
• Lazar GA, Dang W, Karki S, et al. Engineered antibody Fc variants with enhanced effector function. Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4005–4010.
   PubMed Web of Science ®Google Scholar
• Jurczak W, Zinzani PL, Hess G, et al. A phase iia, open-label, multicenter study of single-agent tafasitamab (MOR208), an Fc-Optimized anti-CD19 antibody, in patients with relapsed or refractory B-Cell non-hodgkin’s lymphoma: long-term follow-up, final analysis. Blood. 2019;134(Supplement_1):4078–4078. doi: 10.1182/blood-2019-124297
   Web of Science ®Google Scholar
• Duell J, Maddocks KJ, González-Barca E, et al. Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma. Haematologica. 2021 Sep 01;106(9):2417–2426.
   PubMed Web of Science ®Google Scholar
• Duell J, Obr A, Augustin M, et al. CD19 expression is maintained in DLBCL patients after treatment with tafasitamab plus lenalidomide in the L-MIND study. Leuk Lymphoma. 2022 Feb;63(2):468–472.
   PubMed Web of Science ®Google Scholar
• Morschhauser FA, Cartron G, Thieblemont C, et al. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large B-Cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013;31(23):2912–2919. doi: 10.1200/JCO.2012.46.9585
   PubMed Web of Science ®Google Scholar
• Mössner E, Brünker P, Moser S, et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell–mediated B-cell cytotoxicity. Blood. 2010;115(22):4393–4402. doi: 10.1182/blood-2009-06-225979
   PubMed Web of Science ®Google Scholar
• Houot R, Cartron G, Bijou F, et al. Obinutuzumab plus Lenalidomide (GALEN) for the treatment of relapse/refractory aggressive lymphoma: a phase II LYSA study. Leukemia. 2019 Mar;33(3):776–780.
   PubMed Web of Science ®Google Scholar
• Herbaux C, Casasnovas O, Feugier P, et al. Atezolizumab + obinutuzumab + venetoclax in patients with relapsed or refractory diffuse large B-cell Lymphomas (R/R DLBCL): primary analysis of a phase II trial from LYSA. J Clin Oncol. 2020 2020 Mar 20;38(15_suppl):8053–8053. doi: 10.1200/JCO.2020.38.15_suppl.8053
   Web of Science ®Google Scholar
• Cherng HJ, Alig S, Oki Y, et al. A phase 1/2 study of lenalidomide and obinutuzumab with CHOP for newly diagnosed DLBCL. Blood Adv. 2022 Nov 14;7(7):1137–1145.
   Web of Science ®Google Scholar
• Sehn LH, Herrera AF, Flowers CR, et al. Polatuzumab vedotin in relapsed or refractory diffuse large B-Cell lymphoma. J Clin Oncol. 2020 Jan 10;38(2):155–165.
   PubMed Web of Science ®Google Scholar
• Sehn LH, Hertzberg M, Opat S, et al. Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory DLBCL: survival update and new extension cohort data. Blood Adv. 2022 Jan 25;6(2):533–543.
   PubMed Web of Science ®Google Scholar
• Caimi PF, Ai W, Alderuccio JP, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):790–800.
   PubMed Web of Science ®Google Scholar
• Kingsley E, Grosicki S, Kwiatek M, et al. ABCL-320 initial safety run-in results of the phase 3 LOTIS-5 trial: novel combination of loncastuximab tesirine with rituximab (lonca-R) versus immunochemotherapy in patients with R/R DLBCL. Clin Lymphoma Myeloma Leukemia. 2022 2022 Oct 1;22:S372.
   Web of Science ®Google Scholar
• Carlo-Stella C, Zinzani PLL, Janakiram M, et al. Planned interim analysis of a phase 2 study of loncastuximab tesirine plus ibrutinib in patients with advanced diffuse large b-cell lymphoma (LOTIS-3). Blood. 2021;138(Supplement 1):54–54. doi: 10.1182/blood-2021-147765
   Google Scholar
• Thapa B, Caimi PF, Ardeshna KM, et al. CD19 antibody-drug conjugate therapy in DLBCL does not preclude subsequent responses to CD19-directed CAR T-cell therapy. Blood Adv. 2020 Aug 25;4(16):3850–3852.
   PubMed Web of Science ®Google Scholar
• Caimi PF, Ardeshna KM, Reid E, et al. The AntiCD19 antibody drug immunoconjugate loncastuximab achieves responses in DLBCL relapsing after AntiCD19 CAR-T cell therapy. Clin Lymphoma Myeloma Leuk. 2022 May;22(5):e335–e339.
   PubMed Web of Science ®Google Scholar
• Budde LE, Assouline S, Sehn LH, et al. Single-agent mosunetuzumab shows durable complete responses in patients with relapsed or refractory B-Cell lymphomas: phase i dose-escalation study. J Clin Oncol. 2022 Feb 10;40(5):481–491.
   PubMed Web of Science ®Google Scholar
• González Barca E. Role of bispecific antibodies in relapsed/refractory diffuse large B-Cell lymphoma in the CART era. Front Immunol. 2022;13:909008. doi: 10.3389/fimmu.2022.909008
   PubMed Web of Science ®Google Scholar
• Dickinson MJ, Carlo-Stella C, Morschhauser F, et al. Glofitamab for relapsed or refractory diffuse large B-Cell Lymphoma. N Engl J Med. 2022 Dec 15;387(24):2220–2231.
   PubMed Web of Science ®Google Scholar
• Thieblemont C, Phillips T, Ghesquieres H, et al. Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-Cell-engaging antibody, in relapsed or refractory large b-cell lymphoma: dose expansion in a phase I/II trial. J Clin Oncol. 2023 Apr 20;41(12):2238–2247.
   PubMed Web of Science ®Google Scholar
• Viardot A, Goebeler ME, Hess G, et al. Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma. Blood. 2016 Mar 17;127(11):1410–1416.
   PubMed Web of Science ®Google Scholar
• Katz DA, Morris JD, Chu MP, et al. Open-label, phase 2 study of blinatumomab after frontline R-chemotherapy in adults with newly diagnosed, high-risk DLBCL. Leuk Lymphoma. 2022 Sep;63(9):2063–2073.
   PubMed Web of Science ®Google Scholar
• Mead MD, Popplewell LL, Subklewe M, et al. PHASE I STUDY of the CD19/CD3 half-life extended bite® molecule amg 562 in relapsed/refractory diffuse large b cell lymphoma, mantle cell lymphoma and follicular lymphoma. Hematol Oncol. 2021;39(S2). doi: 10.1002/hon.87_2881
   Google Scholar
• Zhao Y, Aldoss I, Qu C, et al. Tumor-intrinsic and -extrinsic determinants of response to blinatumomab in adults with B-ALL. Blood. 2021 Jan 28;137(4):471–484.
   PubMed Web of Science ®Google Scholar
• Philipp N, Kazerani M, Nicholls A, et al. T-cell exhaustion induced by continuous bispecific molecule exposure is ameliorated by treatment-free intervals. Blood. 2022 Sep 8;140(10):1104–1118.
   PubMed Web of Science ®Google Scholar
• Giri P, Patil S, Ratnasingam S, et al. Results from a phase 1b study of blinatumomab-pembrolizumab combination in adults with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). J Clin Oncol. 2022;40(16_suppl):e19584–e19584. doi: 10.1200/JCO.2022.40.16_suppl.e19584
   Web of Science ®Google Scholar
• Chong EA, Melenhorst JJ, Lacey SF, et al. PD-1 blockade modulates chimeric antigen receptor (CAR)-modified T cells: refueling the CAR. Blood. 2017 Feb 23;129(8):1039–1041.
   PubMed Web of Science ®Google Scholar
• Zhang L, Zhang W, Zhou D. Long-term treatment response to PD-1 blockade therapy in a patient with DLBCL relapsed after anti-CD19 chimeric antigen receptor T cell treatment. Ann Hematol. 2021 Jan;100(1):289–291. doi: 10.1007/s00277-020-03993-9
   PubMed Web of Science ®Google Scholar
• Ghoneim HE, Fan Y, Moustaki A, et al. De Novo epigenetic programs inhibit PD-1 blockade-mediated T cell rejuvenation. Cell. 2017 Jun 29;170(1):142–157.e19.
   PubMed Web of Science ®Google Scholar
• Jalil AR, Andrechak JC, Discher DE. Macrophage checkpoint blockade: results from initial clinical trials, binding analyses, and CD47-SIRPα structure-function. Antib Ther. 2020 Apr;3(2):80–94. doi: 10.1093/abt/tbaa006
   PubMedGoogle Scholar
• Tseng D, Volkmer JP, Willingham SB, et al. Anti-CD47 antibody-mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response. Proc Natl Acad Sci U S A. 2013 Jul 02;110(27):11103–11108.
   PubMed Web of Science ®Google Scholar
• Advani R, Flinn I, Popplewell L, et al. CD47 blockade by Hu5F9-G4 and rituximab in non-hodgkin’s lymphoma. N Engl J Med. 2018 Nov 1;379(18):1711–1721.
   PubMed Web of Science ®Google Scholar
• Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019 01;20(1):31–42. doi: 10.1016/S1470-2045(18)30864-7
   PubMed Web of Science ®Google Scholar
• Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-Cell Lymphoma. N Engl J Med. 2019 Jan 03;380(1):45–56.
   PubMed Web of Science ®Google Scholar
• Oluwole OO, Kersten MJ, Miklos DB, et al. Primary overall survival analysis of the phase 3 randomized ZUMA-7 study of axicabtagene ciloleucel versus standard-of-care therapy in relapsed/refractory large B-cell lymphoma. J Clin Oncol. 2023;41(17_suppl):LBA107–LBA107. doi: 10.1200/JCO.2023.41.17_suppl.LBA107
   Google Scholar
• Sworder BJ, Kurtz DM, Alig SK, et al. Determinants of resistance to engineered T cell therapies targeting CD19 in large B cell lymphomas. Cancer Cell. 2023 Jan 9;41(1):210–225 e5.
   PubMed Web of Science ®Google Scholar
• Lemoine J, Ruella M, Houot R. Born to survive: how cancer cells resist CAR T cell therapy. J Hematol Oncol. 2021 Nov 22;14(1):199.
   PubMed Web of Science ®Google Scholar
• Jain MD, Zhao H, Wang X, et al. Tumor interferon signaling and suppressive myeloid cells are associated with CAR T-cell failure in large B-cell lymphoma. Blood. 2021 May 13;137(19):2621–2633.
   PubMed Web of Science ®Google Scholar
• Rafiq S, Hackett CS, Brentjens RJ. Engineering strategies to overcome the current roadblocks in CAR T cell therapy. Nat Rev Clin Oncol. 2020 Mar;17(3):147–167. doi: 10.1038/s41571-019-0297-y
   PubMed Web of Science ®Google Scholar
• Guedan S, Calderon H, Posey AD, et al. Engineering and design of chimeric antigen receptors. Mol Ther Methods Clin Dev. 2019 Mar 15;12:145–156.
   PubMed Web of Science ®Google Scholar
• Locke FL, Rossi JM, Neelapu SS, et al. Tumor burden, inflammation, and product attributes determine outcomes of axicabtagene ciloleucel in large B-cell lymphoma. Blood Adv. 2020 Oct 13;4(19):4898–4911.
   PubMed Web of Science ®Google Scholar
• Awasthi R, Pacaud L, Waldron E, et al. Tisagenlecleucel cellular kinetics, dose, and immunogenicity in relation to clinical factors in relapsed/refractory DLBCL. Blood Adv. 2020 Feb 11;4(3):560–572.
   PubMed Web of Science ®Google Scholar
• Xu Y, Zhang M, Ramos CA, et al. Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15. Blood. 2014 Jun 12;123(24):3750–3759.
   PubMed Web of Science ®Google Scholar
• Deng Q, Han G, Puebla-Osorio N, et al. Characteristics of anti-CD19 CAR T cell infusion products associated with efficacy and toxicity in patients with large B cell lymphomas. Nat Med. 2020 Dec;26(12):1878–1887.
   PubMed Web of Science ®Google Scholar
• Rossi J, Paczkowski P, Shen YW, et al. Preinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells are associated with clinical outcomes in NHL. Blood. 2018 Aug 23;132(8):804–814.
   PubMed Web of Science ®Google Scholar
• Neelapu SS, Dickinson M, Munoz J, et al. Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. Nat Med. 2022 Apr;28(4):735–742.
   PubMed Web of Science ®Google Scholar
• Depil S, Duchateau P, Grupp SA, et al. ‘Off-the-shelf’ allogeneic CAR T cells: development and challenges. Nat Rev Drug Discov. 2020 Mar;19(3):185–199.
   PubMed Web of Science ®Google Scholar
• Lekakis LJ, Locke FL, Tees M, et al. ALPHA2 study: aLLO-501A allogeneic CAR T in LBCL, updated results continue to show encouraging safety and efficacy with consolidation dosing. Blood. 2021;138(Supplement 1):649–649. doi: 10.1182/blood-2021-146045
   PubMedGoogle Scholar
• Locke FL, Malik S, Tees MT, et al. First-in-human data of ALLO-501A, an allogeneic chimeric antigen receptor (CAR) T-cell therapy and ALLO-647 in relapsed/refractory large B-cell lymphoma (R/R LBCL): aLPHA2 study. J Clin Oncol. 2021;39(15_suppl):2529–2529. doi: 10.1200/JCO.2021.39.15_suppl.2529
   Web of Science ®Google Scholar
• Giles JR, Manne S, Freilich E, et al. Human epigenetic and transcriptional T cell differentiation atlas for identifying functional T cell-specific enhancers. Immunity. 2022 Mar 08;55(3):557–574.e7.
   PubMed Web of Science ®Google Scholar
• Blank CU, Haining WN, Held W, et al. Defining ‘T cell exhaustion’. Nat Rev Immunol. 2019 11;19(11):665–674. doi: 10.1038/s41577-019-0221-9
   PubMed Web of Science ®Google Scholar
• Berger C, Jensen MC, Lansdorp PM, et al. Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates. J Clin Invest. 2008 Jan;118(1):294–305.
   PubMed Web of Science ®Google Scholar
• Turtle CJ, Hanafi LA, Berger C, et al. CD19 CAR-T cells of defined CD4+: cD8+ composition in adult B cell ALL patients. J Clin Invest. 2016 Jun 01;126(6):2123–2138.
   PubMed Web of Science ®Google Scholar
• Sommermeyer D, Hudecek M, Kosasih PL, et al. Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo. Leukemia. 2016 Feb;30(2):492–500.
   PubMed Web of Science ®Google Scholar
• Petersen CT, Hassan M, Morris AB, et al. Improving T-cell expansion and function for adoptive T-cell therapy using ex vivo treatment with PI3Kδ inhibitors and VIP antagonists. Blood Adv. 2018 Feb 13;2(3):210–223.
   PubMed Web of Science ®Google Scholar
• Long AH, Haso WM, Shern JF, et al. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nat Med. 2015 Jun;21(6):581–590.
   PubMed Web of Science ®Google Scholar
• Zhou J, Jin L, Wang F, et al. Chimeric antigen receptor T (CAR-T) cells expanded with IL-7/IL-15 mediate superior antitumor effects. Protein Cell. 2019 Oct;10(10):764–769.
   PubMed Web of Science ®Google Scholar
• Alizadeh D, Wong RA, Yang X, et al. IL15 enhances CAR-T cell antitumor activity by reducing mTORC1 activity and preserving their stem cell memory phenotype. Cancer Immunol Res. 2019 May;7(5):759–772.
   PubMed Web of Science ®Google Scholar
• Kranz E, Kuhlmann CJ, Chan J, et al. Efficient derivation of chimeric-antigen receptor-modified T. Front Immunol. 2022;13:877682. doi: 10.3389/fimmu.2022.877682
   PubMed Web of Science ®Google Scholar
• Sabatino M, Hu J, Sommariva M, et al. Generation of clinical-grade CD19-specific CAR-modified CD8+ memory stem cells for the treatment of human B-cell malignancies. Blood. 2016 Jul 28;128(4):519–528.
   PubMed Web of Science ®Google Scholar
• Mo F, Yu Z, Li P, et al. An engineered IL-2 partial agonist promotes CD8. Nature. 2021 09;597(7877):544–548. doi: 10.1038/s41586-021-03861-0
   PubMed Web of Science ®Google Scholar
• Zhang Q, Ding J, Sun S, et al. Akt inhibition at the initial stage of CAR-T preparation enhances the CAR-positive expression rate, memory phenotype and in vivo efficacy. Am J Cancer Res. 2019;9(11):2379–2396.
   PubMed Web of Science ®Google Scholar
• Zhang H, Hu Y, Shao M, et al. Dasatinib enhances anti-leukemia efficacy of chimeric antigen receptor T cells by inhibiting cell differentiation and exhaustion. J Hematol Oncol. 2021 Jul 21;14(1):113.
   PubMed Web of Science ®Google Scholar
• Mestermann K, Giavridis T, Weber J, et al. The tyrosine kinase inhibitor dasatinib acts as a pharmacologic on/off switch for CAR T cells. Sci Transl Med. 2019 Jul 3;11(499). doi: 10.1126/scitranslmed.aau5907
   PubMed Web of Science ®Google Scholar
• Wang X, Naranjo A, Brown CE, et al. Phenotypic and functional attributes of lentivirus-modified CD19-specific human CD8+ central memory T cells manufactured at clinical scale. J Immunother. 2012;35(9):689–701. doi: 10.1097/CJI.0b013e318270dec7
   PubMed Web of Science ®Google Scholar
• Wang X, Popplewell LL, Wagner JR, et al. Phase 1 studies of central memory-derived CD19 CAR T-cell therapy following autologous HSCT in patients with B-cell NHL. Blood. 2016 Jun 16;127(24):2980–2990.
   PubMed Web of Science ®Google Scholar
• Li L, Li Q, Yan ZX, et al. Transgenic expression of IL-7 regulates CAR-T cell metabolism and enhances in vivo persistence against tumor cells. Sci Rep. 2022 Jul 22;12(1):12506.
   PubMed Web of Science ®Google Scholar
• Hurton LV, Singh H, Najjar AM, et al. Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells. Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):E7788–E7797.
   PubMed Web of Science ®Google Scholar
• Fraietta JA, Nobles CL, Sammons MA, et al. Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells. Nature. 2018 Jun;558(7709):307–312.
   PubMed Web of Science ®Google Scholar
• BATF knockout in CAR T cells prevents exhaustion in solid tumors. Cancer Discovery. 2022;12(12):OF9–OF9. doi: 10.1158/2159-8290.CD-RW2022-188
   Google Scholar
• Seo H, Chen J, González-Avalos E, et al. TOX and TOX2 transcription factors cooperate with NR4A transcription factors to impose CD8 + T cell exhaustion. Proc Natl Acad Sci U S A. 2019 Jun 18;116(25):12410–12415.
   PubMed Web of Science ®Google Scholar
• Kumar J, Kumar R, Kumar Singh A, et al. Deletion of Cbl-b inhibits CD8 + T-cell exhaustion and promotes CAR T-cell function. J Immunother Cancer. 2021 Jan;9(1):e001688.
   PubMed Web of Science ®Google Scholar
• Zhang J, Hu Y, Yang J, et al. Non-viral, specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL. Nature. 2022 Sep;609(7926):369–374.
   PubMed Web of Science ®Google Scholar
• Liu X, Zhang Y, Li K, et al. A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma. Transl Oncol. 2021 Jul;14(7):101085.
   PubMed Web of Science ®Google Scholar
• Zou F, Lu L, Liu J, et al. Engineered triple inhibitory receptor resistance improves anti-tumor CAR-T cell performance via CD56. Nat Commun. 2019 Sep 11;10(1):4109.
   PubMedGoogle Scholar
• Tang N, Cheng C, Zhang X, et al. TGF-β inhibition via CRISPR promotes the long-term efficacy of CAR T cells against solid tumors. JCI Insight. 2020 Feb 27;5(4). doi: 10.1172/jci.insight.133977
   Web of Science ®Google Scholar
• Weber EW, Parker KR, Sotillo E, et al. Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling. Science. 2021 Apr 2;372(6537). doi: 10.1126/science.aba1786
   PubMed Web of Science ®Google Scholar
• Plaks V, Rossi JM, Chou J, et al. CD19 target evasion as a mechanism of relapse in large B-cell lymphoma treated with axicabtagene ciloleucel. Blood. 2021 Sep 23;138(12):1081–1085.
   PubMed Web of Science ®Google Scholar
• Hamieh M, Dobrin A, Cabriolu A, et al. CAR T cell trogocytosis and cooperative killing regulate tumour antigen escape. Nature. 2019 Apr;568(7750):112–116.
   PubMed Web of Science ®Google Scholar
• Spiegel JY, Patel S, Muffly L, et al. CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nat Med. 2021 Aug;27(8):1419–1431.
   PubMed Web of Science ®Google Scholar
• Upadhyay R, Boiarsky JA, Pantsulaia G, et al. A critical role for fas-mediated off-target tumor killing in T-cell immunotherapy. Cancer Discov. 2021 Mar;11(3):599–613.
   PubMed Web of Science ®Google Scholar
• Scholler N, Perbost R, Locke FL, et al. Tumor immune contexture is a determinant of anti-CD19 CAR T cell efficacy in large B cell lymphoma. Nat Med. 2022 Aug 29;28(9):1872–1882. doi: 10.1038/s41591-022-01916-x
   PubMed Web of Science ®Google Scholar
• Jain MD, Ziccheddu B, Coughlin CA, et al. Whole-genome sequencing reveals complex genomic features underlying anti-CD19 CAR T-cell treatment failures in lymphoma. Blood. 2022;140(5):491–503. doi: 10.1182/blood.2021015008
   PubMed Web of Science ®Google Scholar
• Boulch M, Cazaux M, Loe-Mie Y, et al. A cross-talk between CAR T cell subsets and the tumor microenvironment is essential for sustained cytotoxic activity. Sci Immunol. 2021 Mar 26;6(57). doi: 10.1126/sciimmunol.abd4344
   PubMed Web of Science ®Google Scholar
• Rodriguez-Garcia A, Lynn RC, Poussin M, et al. CAR-T cell-mediated depletion of immunosuppressive tumor-associated macrophages promotes endogenous antitumor immunity and augments adoptive immunotherapy. Nat Commun. 2021 Feb 9;12(1):877.
   PubMed Web of Science ®Google Scholar
• Chmielewski M, Kopecky C, Hombach AA, et al. IL-12 release by engineered T cells expressing chimeric antigen receptors can effectively Muster an antigen-independent macrophage response on tumor cells that have shut down tumor antigen expression. Cancer Res. 2011 Sep 1;71(17):5697–5706.
   PubMed Web of Science ®Google Scholar
• Ma L, Dichwalkar T, Chang JYH, et al. Enhanced CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptor. Science. 2019 Jul 12;365(6449):162–168.
   PubMed Web of Science ®Google Scholar
• Sampson JH, Choi BD, Sanchez-Perez L, et al. EGFRvIII Mcar-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss. Clin Cancer Res. 2014 Feb 15;20(4):972–984.
   PubMed Web of Science ®Google Scholar
• Adachi K, Kano Y, Nagai T, et al. IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor. Nat Biotechnol. 2018 Apr;36(4):346–351.
   PubMed Web of Science ®Google Scholar
• Spear P, Barber A, Sentman CL. Collaboration of chimeric antigen receptor (CAR)-expressing T cells and host T cells for optimal elimination of established ovarian tumors. Oncoimmunology. 2013 Apr 1;2(4):e23564. doi: 10.4161/onci.23564
   PubMed Web of Science ®Google Scholar
• Brossart P. The role of antigen spreading in the efficacy of immunotherapies. Clin Cancer Res. 2020 Sep 1;26(17):4442–4447. doi: 10.1158/1078-0432.CCR-20-0305
   PubMed Web of Science ®Google Scholar
• Gardner RA, Finney O, Annesley C, et al. Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood. 2017 Jun 22;129(25):3322–3331. doi: 10.1182/blood-2017-02-769208
   PubMed Web of Science ®Google Scholar
• Cazaux M, Grandjean CL, Lemaître F, et al. Single-cell imaging of CAR T cell activity in vivo reveals extensive functional and anatomical heterogeneity. J Exp Med. 2019 May 6;216(5):1038–1049. doi: 10.1084/jem.20182375
   PubMed Web of Science ®Google Scholar
• Michonneau D, Sagoo P, Breart B, et al. The PD-1 axis enforces an anatomical segregation of CTL activity that creates tumor niches after allogeneic hematopoietic stem cell transplantation. Immunity. 2016 Jan 19;44(1):143–154. doi: 10.1016/j.immuni.2015.12.008
   PubMed Web of Science ®Google Scholar
• Chen PH, Lipschitz M, Weirather JL, et al. Activation of CAR and non-CAR T cells within the tumor microenvironment following CAR T cell therapy. JCI Insight. 2020 Jun 18;5(12). doi: 10.1172/jci.insight.134612
   Web of Science ®Google Scholar
• Hirayama AV, Gauthier J, Hay KA, et al. The response to lymphodepletion impacts PFS in patients with aggressive non-Hodgkin lymphoma treated with CD19 CAR T cells. Blood. 2019 Apr 25;133(17):1876–1887. doi: 10.1182/blood-2018-11-887067
   PubMed Web of Science ®Google Scholar
• Yoshimura T. The chemokine MCP-1 (CCL2) in the host interaction with cancer: a foe or ally? Cell Mol Immunol. 2018 Apr;15(4):335–345. doi: 10.1038/cmi.2017.135
   PubMed Web of Science ®Google Scholar
• Brown CE, Vishwanath RP, Aguilar B, et al. Tumor-derived chemokine MCP-1/CCL2 is sufficient for mediating tumor tropism of adoptively transferred T cells. J Immunol. 2007 Sep 1;179(5):3332–3341. doi: 10.4049/jimmunol.179.5.3332
   PubMed Web of Science ®Google Scholar
• ElKassar N, Gress RE. An overview of IL-7 biology and its use in immunotherapy. J Immunotoxicol. 2010 Mar;7(1):1–7. doi: 10.3109/15476910903453296
   PubMed Web of Science ®Google Scholar
• Carrette F, Surh CD. IL-7 signaling and CD127 receptor regulation in the control of T cell homeostasis. Semin Immunol. 2012 Jun;24(3):209–217. doi: 10.1016/j.smim.2012.04.010
   PubMed Web of Science ®Google Scholar
• Kimura MY, Pobezinsky LA, Guinter TI, et al. IL-7 signaling must be intermittent, not continuous, during CD8+ T cell homeostasis to promote cell survival instead of cell death. Nat Immunol. 2013 Feb;14(2):143–151.
   PubMed Web of Science ®Google Scholar
• Neelapu SS. CAR-T efficacy: is conditioning the key? Blood. 2019 Apr 25;133(17):1799–1800. doi: 10.1182/blood-2019-03-900928
   PubMed Web of Science ®Google Scholar
• Ghilardi G, Chong EA, Svoboda J, et al. Bendamustine is safe and effective for lymphodepletion before tisagenlecleucel in patients with refractory or relapsed large B-cell lymphomas. Ann Oncol. 2022 Sep;33(9):916–928.
   PubMed Web of Science ®Google Scholar
• Jain N, Roboz GJ, Konopleva M, et al. Preliminary results of balli-01: a phase I study of UCART22 (allogeneic engineered T-cells expressing anti-CD22 Chimeric Antigen Receptor) in adult patients with relapsed or refractory (R/R) CD22+ B-Cell acute lymphoblastic leukemia (B-ALL). Blood. 2020;136(Supplement 1):7–8. doi: 10.1182/blood-2020-138594
   Google Scholar
• Pegram HJ, Lee JC, Hayman EG, et al. Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning. Blood. 2012 May 3;119(18):4133–4141. doi: 10.1182/blood-2011-12-400044
   PubMed Web of Science ®Google Scholar
• Yeku OO, Purdon TJ, Koneru M, et al. Armored CAR T cells enhance antitumor efficacy and overcome the tumor microenvironment. Sci Rep. 2017 Sep 5;7(1):10541. doi: 10.1038/s41598-017-10940-8
   PubMed Web of Science ®Google Scholar
• Kueberuwa G, Kalaitsidou M, Cheadle E, et al. CD19 CAR T cells expressing IL-12 eradicate lymphoma in fully lymphoreplete mice through induction of host immunity. Mol Ther Oncolytics. 2018 Mar 30;8:41–51. doi: 10.1016/j.omto.2017.12.003
   PubMed Web of Science ®Google Scholar
• Hoyos V, Savoldo B, Quintarelli C, et al. Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia. 2010 Jun;24(6):1160–1170.
   PubMed Web of Science ®Google Scholar
• Avanzi MP, Yeku O, Li X, et al. Engineered tumor-targeted T cells mediate enhanced anti-tumor efficacy both directly and through activation of the endogenous immune system. Cell Rep. 2018 May 15;23(7):2130–2141. doi: 10.1016/j.celrep.2018.04.051
   PubMed Web of Science ®Google Scholar
• Luo H, Su J, Sun R, et al. Coexpression of IL7 and CCL21 increases efficacy of CAR-T cells in solid tumors without requiring preconditioned lymphodepletion. Clin Cancer Res. 2020 Oct 15;26(20):5494–5505. doi: 10.1158/1078-0432.CCR-20-0777
   PubMed Web of Science ®Google Scholar
• Conde E, Vercher E, Soria-Castellano M, et al. Epitope spreading driven by the joint action of CART cells and pharmacological STING stimulation counteracts tumor escape via antigen-loss variants. J Immunother Cancer. 2021 Nov;9(11):e003351.
   PubMed Web of Science ®Google Scholar
• Steen CB, Luca BA, Esfahani MS, et al. The landscape of tumor cell states and ecosystems in diffuse large B cell lymphoma. Cancer Cell. 2021 Oct 11;39(10):1422–1437 e10. doi: 10.1016/j.ccell.2021.08.011
   PubMed Web of Science ®Google Scholar
• Kotlov N, Bagaev A, Revuelta MV, et al. Clinical and biological subtypes of B-cell lymphoma revealed by microenvironmental signatures. Cancer Discov. 2021 Jun;11(6):1468–1489.
   PubMed Web of Science ®Google Scholar
• Wright GW, Huang DW, Phelan JD, et al. A probabilistic classification tool for genetic subtypes of diffuse large b cell lymphoma with therapeutic implications. Cancer Cell. 2020 Apr 13;37(4):551–568 e14. doi: 10.1016/j.ccell.2020.03.015
   PubMed Web of Science ®Google Scholar
• Reddy A, Zhang J, Davis NS, et al. Genetic and functional drivers of diffuse large B cell lymphoma. Cell. 2017 Oct 5;171(2):481–494 e15. doi: 10.1016/j.cell.2017.09.027
   PubMed Web of Science ®Google Scholar
• Schmitz R, Wright GW, Huang DW, et al. Genetics and pathogenesis of diffuse large B-Cell lymphoma. N Engl J Med. 2018 2018 Apr 12;378(15):1396–1407. doi: 10.1056/NEJMoa1801445
   PubMed Web of Science ®Google Scholar
• Yang Y, Shaffer AL 3rd, Emre NC, et al. Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma. Cancer Cell. 2012 Jun 12;21(6):723–737. doi: 10.1016/j.ccr.2012.05.024
   PubMed Web of Science ®Google Scholar
• Wilson WH, Wright GW, Huang DW, et al. Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL. Cancer Cell. 2021 Dec 13;39(12):1643–1653 e3. doi: 10.1016/j.ccell.2021.10.006
   PubMed Web of Science ®Google Scholar
• Sharma N, Reagan PM, Liesveld JL. Cytopenia after CAR-T cell therapy—A brief review of a complex problem. Cancers (Basel). 2022 Mar 15;14(6):1501. doi: 10.3390/cancers14061501
   PubMed Web of Science ®Google Scholar