1,558
Views
5
CrossRef citations to date
0
Altmetric
Review

Investigational CD33-targeted therapeutics for acute myeloid leukemia

Pages 339-348 | Received 26 Nov 2017, Accepted 12 Mar 2018, Published online: 15 Mar 2018

References

  • Döhner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373(12):1136–1152.
  • Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424–447.
  • Walter RB, Appelbaum FR, Estey EH, et al. Acute myeloid leukemia stem cells and CD33-targeted immunotherapy. Blood. 2012;119(26):6198–6208.
  • Laszlo GS, Estey EH, Walter RB. The past and future of CD33 as therapeutic target in acute myeloid leukemia. Blood Rev. 2014;28(4):143–153.
  • Cowan AJ, Laszlo GS, Estey EH, et al. Antibody-based therapy of acute myeloid leukemia with gemtuzumab ozogamicin. Front Biosci (Landmark Ed). 2013;18(4):1311–1334.
  • Godwin CD, Gale RP, Walter RB. Gemtuzumab ozogamicin in acute myeloid leukemia. Leukemia. 2017;31(9):1855–1868.
  • Macauley MS, Crocker PR, Paulson JC. Siglec-mediated regulation of immune cell function in disease. Nat Rev Immunol. 2014;14(10):653–666.
  • Feldman EJ, Brandwein J, Stone R, et al. Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia. J Clin Oncol. 2005;23(18):4110–4116.
  • Sekeres MA, Lancet JE, Wood BL, et al. Randomized phase IIb study of low-dose cytarabine and lintuzumab versus low-dose cytarabine and placebo in older adults with untreated acute myeloid leukemia. Haematologica. 2013;98(1):119–128.
  • Borthakur G, Rosenblum MG, Talpaz M, et al. Phase 1 study of an anti-CD33 immunotoxin, humanized monoclonal antibody M195 conjugated to recombinant gelonin (HUM-195/rGEL), in patients with advanced myeloid malignancies. Haematologica. 2013;98(2):217–221.
  • Vitale C, Romagnani C, Falco M, et al. Engagement of p75/AIRM1 or CD33 inhibits the proliferation of normal or leukemic myeloid cells. Proc Natl Acad Sci USA. 1999;96(26):15091–15096.
  • Vitale C, Romagnani C, Puccetti A, et al. Surface expression and function of p75/AIRM-1 or CD33 in acute myeloid leukemias: engagement of CD33 induces apoptosis of leukemic cells. Proc Natl Acad Sci USA. 2001;98(10):5764–5769.
  • Sutherland MK, Yu C, Lewis TS, et al. Anti-leukemic activity of lintuzumab (SGN-33) in preclinical models of acute myeloid leukemia. MAbs. 2009;1(5):481–490.
  • Sutherland MK, Yu C, Anderson M, et al. 5-Azacytidine enhances the anti-leukemic activity of lintuzumab (SGN-33) in preclinical models of acute myeloid leukemia. MAbs. 2010;2(4):440–448.
  • Chan WK, Kung Sutherland M, Li Y, et al. Antibody-dependent cell-mediated cytotoxicity overcomes NK cell resistance in MLL-rearranged leukemia expressing inhibitory KIR ligands but not activating ligands. Clin Cancer Res. 2012;18(22):6296–6305.
  • Caron PC, Co MS, Bull MK, et al. Biological and immunological features of humanized M195 (anti-CD33) monoclonal antibodies. Cancer Res. 1992;52(24):6761–6767.
  • Caron PC, Jurcic JG, Scott AM, et al. A phase 1B trial of humanized monoclonal antibody M195 (anti-CD33) in myeloid leukemia: specific targeting without immunogenicity. Blood. 1994;83(7):1760–1768.
  • Caron PC, Dumont L, Scheinberg DA. Supersaturating infusional humanized anti-CD33 monoclonal antibody HuM195 in myelogenous leukemia. Clin Cancer Res. 1998;4(6):1421–1428.
  • Feldman E, Kalaycio M, Weiner G, et al. Treatment of relapsed or refractory acute myeloid leukemia with humanized anti-CD33 monoclonal antibody HuM195. Leukemia. 2003;17(2):314–318.
  • Jurcic JG, DeBlasio T, Dumont L, et al. Molecular remission induction with retinoic acid and anti-CD33 monoclonal antibody HuM195 in acute promyelocytic leukemia. Clin Cancer Res. 2000;6(2):372–380.
  • Raza A, Jurcic JG, Roboz GJ, et al. Complete remissions observed in acute myeloid leukemia following prolonged exposure to lintuzumab: a phase 1 trial. Leuk Lymphoma. 2009;50(8):1336–1344.
  • Kellner C, Otte A, Cappuzzello E, et al. Modulating cytotoxic effector functions by Fc engineering to improve cancer therapy. Transfus Med Hemother. 2017;44(5):327–336.
  • Romain G, Senyukov V, Rey-Villamizar N, et al. Antibody Fc engineering improves frequency and promotes kinetic boosting of serial killing mediated by NK cells. Blood. 2014;124(22):3241–3249.
  • Vasu S, He S, Cheney C, et al. Decitabine enhances anti-CD33 monoclonal antibody BI 836858-mediated natural killer ADCC against AML blasts. Blood. 2016;127(23):2879–2889.
  • Mårlind J, Kaspar M, Trachsel E, et al. Antibody-mediated delivery of interleukin-2 to the stroma of breast cancer strongly enhances the potency of chemotherapy. Clin Cancer Res. 2008;14(20):6515–6524.
  • Gutbrodt KL, Schliemann C, Giovannoni L, et al. Antibody-based delivery of interleukin-2 to neovasculature has potent activity against acute myeloid leukemia. Sci Transl Med. 2013;5(201):201ra118.
  • Schliemann C, Gutbrodt KL, Kerkhoff A, et al. Targeting interleukin-2 to the bone marrow stroma for therapy of acute myeloid leukemia relapsing after allogeneic hematopoietic stem cell transplantation. Cancer Immunol Res. 2015;3(5):547–556.
  • Lapusan S, Vidriales MB, Thomas X, et al. Phase I studies of AVE9633, an anti-CD33 antibody–maytansinoid conjugate, in adult patients with relapsed/refractory acute myeloid leukemia. Invest New Drugs. 2012;30(3):1121–1131.
  • Kung Sutherland MS, Walter RB, Jeffrey SC, et al. SGN-CD33A: a novel CD33-targeting antibody–drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML. Blood. 2013;122(8):1455–1463.
  • Stein AM, Walter RB, Erba HP, et al. A phase 1 trial of vadastuximab talirine as monotherapy in patients with CD33positive acute myeloid leukemia. Blood. 2018;131(4):387–396.
  • Ravandi F, Stein A, Erba H, et al. Vadastuximab talirine plus hypomethylating agents: a well-tolerated regimen with high remission rate in frontline older patients with acute myeloid leukemia [abstract #P201]. Haematologica. 2017;102(S2):48–49.
  • Levy MY, Stein AS, Vasu S, et al. A phase 1b study of the combination of vadastuximab talirine and 7+3 induction therapy for patients with newly diagnosed acute myeloid leukemia [abstract #S793]. Haematologica. 2017;102(S2):324.
  • Godwin CD, McDonald GB, Walter RB. Sinusoidal obstruction syndrome following CD33-targeted therapy in acute myeloid leukemia. Blood. 2017;129(16):2330–2332.
  • Whiteman KR, Noordhuis P, Walker R, et al. The antibody–drug conjugate (ADC) IMGN779 is highly active in vitro and in vivo against acute myeloid leukemia (AML) with FLT3-ITD mutations [abstract]. Blood. 2014;124(21):2321.
  • Krystal WM, Walker R, Fishkin N, et al. IMGN779, a CD33-targeted antibody–drug conjugate (ADC) with a novel DNA-alkylating effector molecule, induces DNA damage, cell cycle arrest, and apoptosis in AML cells [abstract]. Blood. 2015;126(23):1366.
  • Miller ML, Fishkin NE, Li W, et al. A new class of antibody–drug conjugates with potent DNA alkylating activity. Mol Cancer Ther. 2016;15(8):1870–1878.
  • Portwood S, Puchalski RA, Walker RM, et al. Combining IMGN779, a novel anti-CD33 antibody–drug conjugate (ADC), with the PARP inhibitor, olaparib, results in enhanced anti-tumor activity in preclinical acute myeloid leukemia (AML) models [abstract]. Blood. 2016;128(22):1645.
  • Adams S, Kelly M, McCarthy R, et al. IMGN779, a next generation CD33-targeting ADC, combines effectively with cytarabine in acute myeloid leukemia (AML) preclinical models, resulting in increased DNA damage response, cell cycle arrests and apoptosis in vitro and prolonged survival in vivo [abstract]. Blood. 2017;130(Suppl 1):1357.
  • Cortes JE, Traer E, Wang ES, et al. IMGN779, a next-generation CD33-targeting antibody–drug conjugate (ADC) demonstrates initial antileukemia activity in patients with relapsed or refractory acute myeloid leukemia [abstract]. Blood. 2017;130(Suppl 1):1312.
  • Wayne AS, Fitzgerald DJ, Kreitman RJ, et al. Immunotoxins for leukemia. Blood. 2014;123(16):2470–2477.
  • Alewine C, Hassan R, Pastan I. Advances in anticancer immunotoxin therapy. Oncologist. 2015;20(2):176–185.
  • Zahaf NI, Schmidt G. Bacterial toxins for cancer therapy. Toxins (Basel). 2017;9:8.
  • Frankel AE, Woo JH, Ahn C, et al. Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients. Blood. 2014;124(3):385–392.
  • Thomas ED, Storb R, Clift RA, et al. Bone-marrow transplantation. N Engl J Med. 1975;292(16):832–843.
  • Clift RA, Buckner CD, Appelbaum FR, et al. Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: a randomized trial of two irradiation regimens. Blood. 1990;76(9):1867–1871.
  • Clift RA, Buckner CD, Appelbaum FR, et al. Long-term follow-up of a randomized trial of two irradiation regimens for patients receiving allogeneic marrow transplants during first remission of acute myeloid leukemia. Blood. 1998;92(4):1455–1456.
  • Scheinberg DA, Lovett D, Divgi CR, et al. A phase I trial of monoclonal antibody M195 in acute myelogenous leukemia: specific bone marrow targeting and internalization of radionuclide. J Clin Oncol. 1991;9(3):478–490.
  • Appelbaum FR, Matthews DC, Eary JF, et al. The use of radiolabeled anti-CD33 antibody to augment marrow irradiation prior to marrow transplantation for acute myelogenous leukemia. Transplantation. 1992;54(5):829–833.
  • Schwartz MA, Lovett DR, Redner A, et al. Dose-escalation trial of M195 labeled with iodine 131 for cytoreduction and marrow ablation in relapsed or refractory myeloid leukemias. J Clin Oncol. 1993;11(2):294–303.
  • Jurcic JG, Caron PC, Nikula TK, et al. Radiolabeled anti-CD33 monoclonal antibody M195 for myeloid leukemias. Cancer Res. 1995;55(23 Suppl):5908s–10s.
  • Burke JM, Caron PC, Papadopoulos EB, et al. Cytoreduction with iodine-131-anti-CD33 antibodies before bone marrow transplantation for advanced myeloid leukemias. Bone Marrow Transplant. 2003;32(6):549–556.
  • Nikula TK, McDevitt MR, Finn RD, et al. Alpha-emitting bismuth cyclohexylbenzyl DTPA constructs of recombinant humanized anti-CD33 antibodies: pharmacokinetics, bioactivity, toxicity and chemistry. J Nucl Med. 1999;40(1):166–176.
  • McDevitt MR, Finn RD, Ma D, et al. Preparation of alpha-emitting 213Bi-labeled antibody constructs for clinical use. J Nucl Med. 1999;40(10):1722–1727.
  • Jurcic JG, Rosenblat TL. Targeted alpha-particle immunotherapy for acute myeloid leukemia. Am Soc Clin Oncol Educ Book. 2014;e126–31.
  • Jurcic JG, Larson SM, Sgouros G, et al. Targeted alpha particle immunotherapy for myeloid leukemia. Blood. 2002;100(4):1233–1239.
  • Rosenblat TL, McDevitt MR, Mulford DA, et al. Sequential cytarabine and alpha-particle immunotherapy with bismuth-213-lintuzumab (HuM195) for acute myeloid leukemia. Clin Cancer Res. 2010;16(21):5303–5311.
  • Jurcic JG, Rosenblat TL, McDevitt MR, et al. Phase I trial of the targeted-particle nano-generator actinium 225 (225Ac)-lintuzumab (anti-CD33; HuM195) in acute myeloid leukemia (AML) [abstract]. Blood. 2011;118(21):768.
  • Jurcic JG, Levy MY, Park JH, et al. Phase I trial of targeted alpha-particle therapy with actinium-225 (225Ac)-lintuzumab and low-dose cytarabine (LDAC) in patients age 60 or older with untreated acute myeloid leukemia (AML) [abstract]. Blood. 2016;128(22):4050.
  • Finn LE, Levy M, Orozco JJ, et al. A phase 2 study of actinium-225 (225Ac)-lintuzumab in older patients with previously untreated acute myeloid leukemia (AML) unfit for intensive chemotherapy [abstract]. Blood. 2017;130(Suppl 1):2638.
  • Carter P. Improving the efficacy of antibody-based cancer therapies. Nat Rev Cancer. 2001;1(2):118–129.
  • Riethmüller G. Symmetry breaking: bispecific antibodies, the beginnings, and 50 years on. Cancer Immun. 2012;12:12.
  • Weiner LM, Murray JC, Shuptrine CW. Antibody-based immunotherapy of cancer. Cell. 2012;148(6):1081–1084.
  • Klinger M, Benjamin J, Kischel R, et al. Harnessing T cells to fight cancer with BiTE(R) antibody constructs–past developments and future directions. Immunol Rev. 2016;270(1):193–208.
  • Yuraszeck T, Kasichayanula S, Benjamin JE. Translation and clinical development of bispecific T-cell engaging antibodies for cancer treatment. Clin Pharmacol Ther. 2017;101(5):634–645.
  • Kontermann RE, Brinkmann U. Bispecific antibodies. Drug Discov Today. 2015;20(7):838–847.
  • Wolach O, Stone RM. Blinatumomab for the treatment of Philadelphia chromosome-negative, precursor B-cell acute lymphoblastic leukemia. Clin Cancer Res. 2015;21(19):4262–4269.
  • Przepiorka D, Ko CW, Deisseroth A, et al. FDA approval: blinatumomab. Clin Cancer Res. 2015;21(18):4035–4039.
  • Brinkmann U, Kontermann RE. The making of bispecific antibodies. MAbs. 2017;9(2):182–212.
  • Uy GL, Godwin J, Rettig MP, et al. Preliminary results of a phase 1 study of flotetuzumab, a CD123 × CD3 bispecific DART protein, in patients with relapsed/refractory acute myeloid leukemia and myelodysplastic syndromes [abstract]. Blood. 2017;130(Suppl 1):637.
  • Friedrich M, Henn A, Raum T, et al. Preclinical characterization of AMG 330, a CD3/CD33-bispecific T-cell-engaging antibody with potential for treatment of acute myelogenous leukemia. Mol Cancer Ther. 2014;13(6):1549–1557.
  • Aigner M, Feulner J, Schaffer S, et al. T lymphocytes can be effectively recruited for ex vivo and in vivo lysis of AML blasts by a novel CD33/CD3-bispecific BiTE antibody construct. Leukemia. 2013;27(5):1107–1115.
  • Krupka C, Kufer P, Kischel R, et al. CD33 target validation and sustained depletion of AML blasts in long-term cultures by the bispecific T-cell-engaging antibody AMG 330. Blood. 2014;123(3):356–365.
  • Laszlo GS, Gudgeon CJ, Harrington KH, et al. Cellular determinants for preclinical activity of a novel CD33/CD3 bispecific T-cell engager (BiTE) antibody, AMG 330, against human AML. Blood. 2014;123(4):554–561.
  • Harrington KH, Gudgeon CJ, Laszlo GS, et al. The broad anti-AML activity of the CD33/CD3 BiTE antibody construct, AMG 330, is impacted by disease stage and risk. PLoS One. 2015;10(8):e0135945.
  • Krupka C, Kufer P, Kischel R, et al. Blockade of the PD-1/PD-L1 axis augments lysis of AML cells by the CD33/CD3 BiTE antibody construct AMG 330: reversing a T-cell-induced immune escape mechanism. Leukemia. 2016;30(2):484–491.
  • Mougiakakos D, Saul D, Braun M, et al. CD33/CD3-bispecific T-cell engating (BiTE) antibody constructs efficiently target monocytic CD14+ HLA-DRlow IDO+ AML-MDSCs [abstract]. Blood. 2017;130(Suppl 1):1363.
  • Laszlo GS, Gudgeon CJ, Harrington KH, et al. T-cell ligands modulate the cytolytic activity of the CD33/CD3 BiTE antibody construct, AMG 330. Blood Cancer J. 2015;5:e340.
  • Feucht J, Kayser S, Gorodezki D, et al. T-cell responses against CD19+ pediatric acute lymphoblastic leukemia mediated by bispecific T-cell engager (BiTE) are regulated contrarily by PD-L1 and CD80/CD86 on leukemic blasts. Oncotarget. 2016;7(47):76902–76919.
  • Correnti CE, Laszlo GS, de van der Schueren WJ, et al. Simultaneous multiple interaction T-cell engaging (SMITE) bispecific antibodies overcome bispecific T-cell engager (BiTE) resistance via CD28 co-stimulation. Leukemia. 2018. doi: 10.1038/s41375-018-0014-3
  • McAleese F, Eser M. RECRUIT-TandAbs: harnessing the immune system to kill cancer cells. Future Oncol. 2012;8(6):687–695.
  • Reusch U, Burkhardt C, Fucek I, et al. A novel tetravalent bispecific TandAb (CD30/CD16A) efficiently recruits NK cells for the lysis of CD30+ tumor cells. MAbs. 2014;6(3):728–739.
  • Reusch U, Duell J, Ellwanger K, et al. A tetravalent bispecific TandAb (CD19/CD3), AFM11, efficiently recruits T cells for the potent lysis of CD19(+) tumor cells. MAbs. 2015;7(3):584–604.
  • Reusch U, Harrington KH, Gudgeon CJ, et al. Characterization of CD33/CD3 tetravalent bispecific tandem diabodies (TandAbs) for the treatment of acute myeloid leukemia. Clin Cancer Res. 2016;22(23):5829–5838.
  • Cheng P, Eksioglu E, Chen X, et al. Immunodepletion of MDSC by AMV564, a novel tetravalent bispecific CD33/CD3 T cell engager restores immune homeostasis in MDS in vitro [abstract]. Blood. 2017;130(Suppl1):51.
  • Wiernik A, Foley B, Zhang B, et al. Targeting natural killer cells to acute myeloid leukemia in vitro with a CD16 × 33 bispecific killer cell engager and ADAM17 inhibition. Clin Cancer Res. 2013;19(14):3844–3855.
  • Gleason MK, Ross JA, Warlick ED, et al. CD16xCD33 bispecific killer cell engager (BiKE) activates NK cells against primary MDS and MDSC CD33+ targets. Blood. 2014;123(19):3016–3026.
  • Miller JS, Felice M, McElmurry R, et al. Trispecific Killer Engagers (TriKEs) that contain IL-15 to make NK cells antigen specific and to sustain their persistence and expansion [abstract]. Blood. 2015;126(23):232.
  • Vallera DA, Felices M, McElmurry R, et al. IL15 Trispecific Killer Engagers (TriKE) make natural killer cells specific to CD33+ targets while also inducing persistence, in vivo expansion, and enhanced function. Clin Cancer Res. 2016;22(14):3440–3450.
  • Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507–1517.
  • Lee DW, Kochenderfer JN, Stetler-Stevenson M, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385(9967):517–528.
  • Batlevi CL, Matsuki E, Brentjens RJ, et al. Novel immunotherapies in lymphoid malignancies. Nat Rev Clin Oncol. 2016;13(1):25–40.
  • Gill S, Maus MV, Porter DL. Chimeric antigen receptor T cell therapy: 25years in the making. Blood Rev. 2016;30(3):157–167.
  • Maude SL, Teachey DT, Porter DL, et al. CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood. 2015;125(26):4017–4023.
  • Budde L, Song JY, Kim Y, et al. Remissions of acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm following treatment with CD123-specific CAR T cells: a first-in-human clinical trial [abstract]. Blood. 2017;130(Suppl 1):811.
  • Wang QS, Wang Y, Lv HY, et al. Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia. Mol Ther. 2015;23(1):184–191.
  • Marin V, Pizzitola I, Agostoni V, et al. Cytokine-induced killer cells for cell therapy of acute myeloid leukemia: improvement of their immune activity by expression of CD33-specific chimeric receptors. Haematologica. 2010;95(12):2144–2152.
  • Dutour A, Marin V, Pizzitola I, et al. In vitro and in vivo antitumor effect of anti-CD33 chimeric receptor-expressing EBV-CTL against CD33+ acute myeloid leukemia. Adv Hematol. 2012;2012:683065.
  • Tettamanti S, Marin V, Pizzitola I, et al. Targeting of acute myeloid leukaemia by cytokine-induced killer cells redirected with a novel CD123-specific chimeric antigen receptor. Br J Haematol. 2013;161(3):389–401.
  • Mardiros A, Dos Santos C, McDonald T, et al. T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia. Blood. 2013;122(18):3138–3148.
  • Pizzitola I, Anjos-Afonso F, Rouault-Pierre K, et al. Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo. Leukemia. 2014;28(8):1596–1605.
  • Gill S, Tasian SK, Ruella M, et al. Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells. Blood. 2014;123(15):2343–2354.
  • O’Hear C, Heiber JF, Schubert I, et al. Anti-CD33 chimeric antigen receptor targeting of acute myeloid leukemia. Haematologica. 2015;100(3):336–344.
  • Kenderian SS, Ruella M, Shestova O, et al. CD33-specific chimeric antigen receptor T cells exhibit potent preclinical activity against human acute myeloid leukemia. Leukemia. 2015;29(8):1637–1647.
  • Rashidi A, Walter RB. Antigen-specific immunotherapy for acute myeloid leukemia: where are we now, and where do we go from here? Expert Rev Hematol. 2016;9(4):335–350.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.