Vaccines targeting ESR1 activating mutations elicit anti-tumor immune responses and suppress estrogen signaling in therapy resistant ER+ breast cancer

References

• Hanker AB, Sudhan DR, Arteaga CL. Overcoming endocrine resistance in breast cancer. Cancer Cell. 2020;37(4):496–10. doi:10.1016/j.ccell.2020.03.009.
   PubMed Web of Science ®Google Scholar
• Haque MM, Desai KV. Pathways to endocrine therapy resistance in breast cancer. Front Endocrinol (Lausanne). 2019;10:573. doi:10.3389/fendo.2019.00573.
   PubMed Web of Science ®Google Scholar
• Gezer U, Bronkhorst AJ, Holdenrieder S. The clinical utility of droplet digital PCR for profiling circulating tumor DNA in breast cancer patients. Diagnostics (Basel). 2022;12(12):3042. doi:10.3390/diagnostics12123042.
   PubMedGoogle Scholar
• Stergiopoulou D, Markou A, Giannopoulou L, Buderath P, Balgkouranidou I, Xenidis N, Kakolyris S, Kasimir-Bauer S, Lianidou E. Detection of ESR1 mutations in primary tumors and plasma cell-free DNA in high-grade serous ovarian carcinoma patients. Cancers Basel. 2022;14(15):3790. doi:10.3390/cancers14153790.
   PubMed Web of Science ®Google Scholar
• Brett JO, Spring LM, Bardia A, Wander SA. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res. 2021;23(1):ARTN 85. doi:10.1186/s13058-021-01462-3.
   Web of Science ®Google Scholar
• Sundaresan TK, Dubash TD, Zheng Z, Bardia A, Wittner BS, Aceto N, Silva EJ, Fox DB, Liebers M, Kapur R. et al. Evaluation of endocrine resistance using ESR1 genotyping of circulating tumor cells and plasma DNA. Breast Cancer Res Treat. 2021;188(1):43–52. doi:10.1007/s10549-021-06270-z.
   PubMed Web of Science ®Google Scholar
• Muendlein A, Geiger K, Gaenger S, Dechow T, Nonnenbroich C, Leiherer A, Drexel H, Gaumann A, Jagla W, Winder T, et al. Significant impact of circulating tumour DNA mutations on survival in metastatic breast cancer patients. Sci Rep. 2021;11(1):6761. doi:10.1038/s41598-021-86238-7.
   PubMed Web of Science ®Google Scholar
• Dustin D, Gu G, Fuqua SAW. ESR1 mutations in breast cancer. Cancer. 2019;125(21):3714–3728. doi:10.1002/cncr.32345.
   PubMed Web of Science ®Google Scholar
• Ahn SG, Bae SJ, Kim Y, Ji JH, Chu C, Kim D, Lee J, Cha YJ, Lee K-A, Jeong J, et al. Primary endocrine resistance of ER+ breast cancer with ESR1 mutations interrogated by droplet digital PCR. NPJ Breast Cancer. 2022;8(1):58. doi:10.1038/s41523-022-00424-y.
   PubMed Web of Science ®Google Scholar
• Jeselsohn R, Bergholz JS, Pun M, Cornwell M, Liu W, Nardone A, Xiao T, Li W, Qiu X, Buchwalter G, et al. Allele-specific chromatin recruitment and therapeutic vulnerabilities of ESR1 activating mutations. Cancer Cell. 2018;33(2):173–86 e175. doi:10.1016/j.ccell.2018.01.004.
   PubMed Web of Science ®Google Scholar
• Gelsomino L Panza S, Giordano C, Barone I, Gu G, Spina E, Catalano S, Fuqua S, Andò S. Mutations in the estrogen receptor alpha hormone binding domain promote stem cell phenotype through notch activation in breast cancer cell lines. Cancer Lett. 2018;428:12–20. doi:10.1016/j.canlet.2018.04.023.
   PubMed Web of Science ®Google Scholar
• Gelsomino L, Gu G, Rechoum Y, Beyer AR, Pejerrey SM, Tsimelzon A, Wang T, Huffman K, Ludlow A, Andò S, et al. ESR1 mutations affect anti-proliferative responses to tamoxifen through enhanced cross-talk with IGF signaling. Breast Cancer Res Treat. 2016;157(2):253–265. doi:10.1007/s10549-016-3829-5.
   PubMed Web of Science ®Google Scholar
• Yamamoto TN, Kishton RJ, Restifo NP. Developing neoantigen-targeted T cell–based treatments for solid tumors. Nat Med. 2019;25(10):1488–99. doi:10.1038/s41591-019-0596-y.
   PubMed Web of Science ®Google Scholar
• Hu Z, Ott PA, Wu CJ. Towards personalized, tumour-specific, therapeutic vaccines for cancer. Nat Rev Immunol. 2018;18(3):168–182. doi:10.1038/nri.2017.131.
   PubMed Web of Science ®Google Scholar
• Crosby EJ, Acharya CR, Haddad A-F, Rabiola CA, Lei G, Wei J-P, Yang X-Y, Wang T, Liu C-X, Wagner KU, et al. Stimulation of Oncogene-specific tumor-infiltrating T cells through combined vaccine and αPD-1 enable sustained antitumor responses against established HER2 breast cancer. Clin Cancer Res. 2020;26(17):4670–81. doi:10.1158/1078-0432.CCR-20-0389.
   PubMed Web of Science ®Google Scholar
• Crosby EJ, Gwin W, Blackwell K, Marcom PK, Chang S, Maecker HT, Broadwater G, Hyslop T, Kim S, Rogatko A, et al. Vaccine-induced memory CD8(+) T cells provide clinical benefit in HER2 expressing breast cancer: a mouse to human translational study. Clin Cancer Res. 2019;25(9):2725–36. doi:10.1158/1078-0432.CCR-18-3102.
   PubMed Web of Science ®Google Scholar
• Hartman ZC, Wei J, Osada T, Glass O, Lei G, Yang X-Y, Peplinski S, Kim D-W, Xia W, Spector N, et al. An adenoviral vaccine encoding full-length inactivated human Her2 exhibits potent immunogenicity and enhanced therapeutic efficacy without oncogenicity. Clin Cancer Res. 2010;16(5):1466–77. doi:10.1158/1078-0432.CCR-09-2549.
   PubMed Web of Science ®Google Scholar
• Kuang Y, Siddiqui B, Hu J, Pun M, Cornwell M, Buchwalter G, Hughes ME, Wagle N, Kirschmeier P, Jänne PA, et al. Unraveling the clinicopathological features driving the emergence of ESR1 mutations in metastatic breast cancer. NPJ Breast Cancer. 2018;4(1):22. doi:10.1038/s41523-018-0075-5.
   PubMedGoogle Scholar
• Fribbens C, Garcia Murillas I, Beaney M, Hrebien S, O’Leary B, Kilburn L, Howarth K, Epstein M, Green E, Rosenfeld N, et al. Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA analysis in metastatic breast cancer. Ann Oncol. 2018;29(1):145–153. doi:10.1093/annonc/mdx483.
   PubMed Web of Science ®Google Scholar
• Cardoso F, McArthur HL, Schmid P, Cortés J, Harbeck N, Telli ML, Cescon DW, O’Shaughnessy J, Fasching P, Shao Z, et al. LBA21 KEYNOTE-756: phase III study of neoadjuvant pembrolizumab (pembro) or placebo (pbo) + chemotherapy (chemo), followed by adjuvant pembro or pbo + endocrine therapy (ET) for early-stage high-risk ER+/HER2– breast cancer. Ann Oncol. 2023;34:S1260–S1261. doi:10.1016/j.annonc.2023.10.011.
   Google Scholar
• Cunningham AL, Garçon N, Leo O, Friedland LR, Strugnell R, Laupèze B, Doherty M, Stern P. Vaccine development: from concept to early clinical testing. Vaccine. 2016;34(52):6655–64. doi:10.1016/j.vaccine.2016.10.016.
   PubMed Web of Science ®Google Scholar
• Schiller JT, Lowy DR. Raising expectations for subunit vaccine. J Infect Dis. 2015;211(9):1373–1375. doi:10.1093/infdis/jiu648.
   PubMed Web of Science ®Google Scholar
• Tsao LC, Crosby EJ, Trotter TN, Agarwal P, Hwang B-J, Acharya C, Shuptrine CW, Wang T, Wei J, Yang X, et al. CD47 blockade augmentation of trastuzumab antitumor efficacy dependent on antibody-dependent cellular phagocytosis. JCI Insight. 2019;4(24). doi:10.1172/jci.insight.131882.
   PubMed Web of Science ®Google Scholar
• Kurebayashi S, Miyashita Y, Hirose T, Kasayama S, Akira S, Kishimoto T. Characterization of mechanisms of interleukin-6 gene repression by estrogen receptor. J Steroid Biochem Mol Biol. 1997;60(1–2):11–17. doi:10.1016/s0960-0760(96)00175-6.
   PubMed Web of Science ®Google Scholar
• Ray A, Prefontaine KE, Ray P. Down-modulation of interleukin-6 gene expression by 17 beta-estradiol in the absence of high affinity DNA binding by the estrogen receptor. J Biol Chem. 1994;269(17):12940–12946. doi:10.1016/S0021-9258(18)99966-7.
   PubMed Web of Science ®Google Scholar
• Chan SR, Vermi W, Luo J, Lucini L, Rickert C, Fowler AM, Lonardi S, Arthur C, Young LJ, Levy DE, et al. STAT1-deficient mice spontaneously develop estrogen receptor α-positive luminal mammary carcinomas. Breast Cancer Res. 2012;14(1):R16. doi:10.1186/bcr3100.
   PubMed Web of Science ®Google Scholar
• Goodman ML, Trinca GM, Walter KR, Papachristou EK, D’Santos CS, Li T, Liu Q, Lai Z, Chalise P, Madan R, et al. Progesterone receptor attenuates STAT1-mediated IFN signaling in breast cancer. J Immunol. 2019;202(10):3076–3086. doi:10.4049/jimmunol.1801152.
   PubMed Web of Science ®Google Scholar
• Morse MA, Crosby EJ, Force J, Osada T, Hobeika AC, Hartman ZC, Berglund P, Smith J, Lyerly HK. Clinical trials of self-replicating RNA-based cancer vaccines. Cancer Gene Ther. 2023;30(6):803–11. doi:10.1038/s41417-023-00587-1.
   PubMed Web of Science ®Google Scholar
• Dailey GP, Crosby EJ, Hartman ZC. Cancer vaccine strategies using self-replicating RNA viral platforms. Cancer Gene Ther. 2023;30(6):794–802. doi:10.1038/s41417-022-00499-6.
   PubMed Web of Science ®Google Scholar
• Saxena M, van der Burg SH, Melief CJM, Bhardwaj N. Therapeutic cancer vaccines. Nat Rev Cancer. 2021;21(6):360–378. doi:10.1038/s41568-021-00346-0.
   PubMed Web of Science ®Google Scholar
• Hollingsworth RE, Jansen K. Turning the corner on therapeutic cancer vaccines. NPJ Vaccines. 2019;4(1):7. doi:10.1038/s41541-019-0103-y.
   PubMed Web of Science ®Google Scholar
• Gonzalez TL, Rae JM, Colacino JA, Richardson RJ. Homology models of mouse and rat estrogen receptor-alpha ligand-binding domain created by in silico mutagenesis of a human template: molecular docking with 17ss-estradiol, diethylstilbestrol, and paraben analogs. Comput Toxicol. 2019;10:1–16. doi:10.1016/j.comtox.2018.11.003.
   PubMedGoogle Scholar
• Lee HJ, Song IH, Park IA, Heo S-H, Kim Y-A, Ahn J-H, Gong G. Differential expression of major histocompatibility complex class I in subtypes of breast cancer is associated with estrogen receptor and interferon signaling. Oncotarget. 2016;7(21):30119–32. doi:10.18632/oncotarget.8798.
   PubMedGoogle Scholar
• Sinn BV, Weber KE, Schmitt WD, Fasching PA, Symmans WF, Blohmer J-U, Karn T, Taube ET, Klauschen F, Marmé F, et al. Human leucocyte antigen class I in hormone receptor-positive, HER2-negative breast cancer: association with response and survival after neoadjuvant chemotherapy. Breast Cancer Res. 2019;21(1):142. doi:10.1186/s13058-019-1231-z.
   PubMed Web of Science ®Google Scholar
• Chung YR, Kim HJ, Jang MH, Park SY. Prognostic value of tumor infiltrating lymphocyte subsets in breast cancer depends on hormone receptor status. Breast Cancer Res Treat. 2017;161(3):409–420. doi:10.1007/s10549-016-4072-9.
   PubMed Web of Science ®Google Scholar
• Liu F, Lang R, Zhao J, Zhang X, Pringle GA, Fan Y, Yin D, Gu F, Yao Z, Fu L, et al. CD8(+) cytotoxic T cell and FOXP3(+) regulatory T cell infiltration in relation to breast cancer survival and molecular subtypes. Breast Cancer Res Treat. 2011;130(2):645–55. doi:10.1007/s10549-011-1647-3.
   PubMed Web of Science ®Google Scholar
• Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22(1):329–360. doi:10.1146/annurev.immunol.22.012703.104803.
   PubMed Web of Science ®Google Scholar
• Giovannetti A, Maselli A, Colasanti T, Rosato E, Salsano F, Pisarri S, Mezzaroma I, Malorni W, Ortona E, Pierdominici M, et al. Autoantibodies to Estrogen receptor α in systemic sclerosis (SSc) as pathogenetic determinants and markers of progression. PloS ONE. 2013;8(9):e74332. doi:10.1371/journal.pone.0074332.
   PubMed Web of Science ®Google Scholar
• Colasanti T, Maselli A, Conti F, Sanchez M, Alessandri C, Barbati C, Vacirca D, Tinari A, Chiarotti F, Giovannetti A, et al. Autoantibodies to estrogen receptor α interfere with T lymphocyte homeostasis and are associated with disease activity in systemic lupus erythematosus. Arthritis & Rheumatism. 2012;64(3):778–87. doi:10.1002/art.33400.
   PubMedGoogle Scholar
• Maselli A, Conti F, Alessandri C, Colasanti T, Barbati C, Vomero M, Ciarlo L, Patrizio M, Spinelli FR, Ortona E, et al. Low expression of estrogen receptor β in T lymphocytes and high serum levels of anti-estrogen receptor α antibodies impact disease activity in female patients with systemic lupus erythematosus. Biol Sex Differ. 2016;7(1):3. doi:10.1186/s13293-016-0057-y.
   PubMedGoogle Scholar
• Quaynor SD, Stradtman EW, Kim H-G, Shen Y, Chorich LP, Schreihofer DA, Layman LC. Delayed puberty and Estrogen Resistance in a woman with Estrogen receptor α variant. N Engl J Med. 2013;369(2):164–71. doi:10.1056/NEJMoa1303611.
   PubMed Web of Science ®Google Scholar
• Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B, Williams TC, Lubahn DB, Korach KS. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med. 1994;331(16):1056–61. doi:10.1056/NEJM199410203311604.
   PubMed Web of Science ®Google Scholar
• Hartman ZC, Poage GM, den Hollander P, Tsimelzon A, Hill J, Panupinthu N, Zhang Y, Mazumdar A, Hilsenbeck SG, Mills GB, et al. Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8. Cancer Res. 2013;73(11):3470–3480. doi:10.1158/0008-5472.CAN-12-4524-T.
   PubMed Web of Science ®Google Scholar
• Hartman ZC, Black EP, Amalfitano A. Adenoviral infection induces a multi-faceted innate cellular immune response that is mediated by the toll-like receptor pathway in A549 cells. Virology. 2007;358(2):357–372. doi:10.1016/j.virol.2006.08.041.
   PubMed Web of Science ®Google Scholar
• Hartman ZC, Wei J, Glass OK, Guo H, Lei G, Yang X-Y, Osada T, Hobeika A, Delcayre A, Le Pecq J-B, et al. Increasing vaccine potency through exosome antigen targeting. Vaccine. 2011;29(50):9361–9367. doi:10.1016/j.vaccine.2011.09.133.
   PubMed Web of Science ®Google Scholar
• Conesa A, Madrigal P, Tarazona S, Gomez-Cabrero D, Cervera A, McPherson A, Szcześniak MW, Gaffney DJ, Elo LL, Zhang X, et al. A survey of best practices for RNA-seq data analysis. Genome Biol. 2016;17(1):13. doi:10.1186/s13059-016-0881-8.
   PubMed Web of Science ®Google Scholar
• Cimen Bozkus C, Blazquez AB, Enokida T, Bhardwaj N. A T-cell-based immunogenicity protocol for evaluating human antigen-specific responses. STAR Protoc. 2021;2(3):100758. doi:10.1016/j.xpro.2021.100758.
   PubMedGoogle Scholar