[Fam-] trastuzumab deruxtecan (DS-8201a)-induced antitumor immunity is facilitated by the anti–CTLA-4 antibody in a mouse model


Autoři: Tomomi Nakayama Iwata aff001;  Kiyoshi Sugihara aff001;  Teiji Wada aff001;  Toshinori Agatsuma aff001
Působiště autorů: Oncology Research Laboratories I, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan aff001
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222280

Souhrn

[Fam-] trastuzumab deruxtecan (DS-8201a) is a HER2 (ERBB2)-targeting antibody-drug conjugate, composed of a HER2-targeting antibody and a topoisomerase I inhibitor, exatecan derivative, that has antitumor effects in preclinical xenograft models and clinical trials. Recently, [fam-] trastuzumab deruxtecan was reported to enhance antitumor immunity and was beneficial in combination with an anti–PD-1 antibody in a mouse model. In this study, the antitumor effect of [fam-] trastuzumab deruxtecan in combination with an anti–CTLA-4 antibody was evaluated. [Fam-] trastuzumab deruxtecan monotherapy had antitumor activity in an immunocompetent mouse model with EMT6 human HER2-expressing mouse breast cancer cells (EMT6-hHER2). [Fam-] trastuzumab deruxtecan in combination with the anti–CTLA-4 antibody induced more potent antitumor activity than that by monotherapy with either agent. The combination therapy increased tumor-infiltrating CD4+ and CD8+ T cells in vivo. Mechanistically, cured mice with treatment of [fam-] trastuzumab deruxtecan and an anti–CTLA-4 antibody completely rejected EMT6-mock cells similar to EMT6-hHER2 cells, and splenocytes from the cured mice responded to both EMT6-hHER2 and EMT6-mock cells as measured by interferon-gamma release. Taken together, these results indicate that antitumor immunity is induced by [fam-] trastuzumab deruxtecan and is facilitated in combination with anti–CTLA-4 antibody.

Klíčová slova:

Antibodies – Cancer treatment – Cytotoxic T cells – Enzyme-linked immunoassays – Flow cytometry – Immunohistochemistry techniques – Mouse models – T cells


Zdroje

1. Ogitani Y, Aida T, Hagihara K, Yamaguchi J, Ishii C, Harada N, et al. DS-8201a, A novel HER2-targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1. Clin Cancer Res. 2016;22(20):5097–5108. doi: 10.1158/1078-0432.CCR-15-2822 27026201

2. Ogitani Y, Hagihara K, Oitate M, Naito H, Agatsuma T. Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody–drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity. Cancer Sci. 2016;107(7):1039–1046. doi: 10.1111/cas.12966 27166974

3. Doi T, Shitara K, Naito Y, Shimomura A, Fujiwara Y, Yonemori K, et al. Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody–drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study. Lancet Oncol. 2017;18(11):1512–1522. doi: 10.1016/S1470-2045(17)30604-6 29037983

4. Tamura K, Tsurutani J, Takahashi S, Iwata H, Krop IE, Redfern C, et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Lancet Oncol. 2019;20(6):816–826. doi: 10.1016/S1470-2045(19)30097-X 31047803

5. Shitara K, Iwata H, Takahashi S, Tamura K, Park H, Modi S, et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. Lancet Oncol. 2019;20(6):827–836. doi: 10.1016/S1470-2045(19)30088-9 31047804

6. Iwata H, Tamura K, Doi T, Tsurutani J, Modi S, Park H, et al. Trastuzumab deruxtecan (DS-8201a) in subjects with HER2-expressing solid tumors: Long-term results of a large phase 1 study with multiple expansion cohorts. J Clin Oncol 2018;36(15_suppl):2501–2501.

7. Bracci L, Schiavoni G, Sistigu A, Belardelli F. Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer. Cell Death Differ. 2014;21(1):15–25. doi: 10.1038/cdd.2013.67 23787994

8. Gerber H-P, Sapra P, Loganzo F, May C. Combining antibody–drug conjugates and immune-mediated cancer therapy: What to expect? Biochem Pharmacol. 2016;102:1–6. doi: 10.1016/j.bcp.2015.12.008 26686577

9. Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10. doi: 10.1016/j.immuni.2013.07.012 23890059

10. Martin K, Müller P, Schreiner J, Prince SS, Lardinois D, Heinzelmann-Schwarz VA, et al. The microtubule-depolymerizing agent ansamitocin P3 programs dendritic cells toward enhanced anti-tumor immunity. Cancer Immunol Immunother. 2014;63(9):925–938. doi: 10.1007/s00262-014-1565-4 24906866

11. McKenzie JA, Mbofung RM, Malu S, Zhang M, Ashkin E, Devi S, et al. The effect of topoisomerase I inhibitors on the efficacy of T-cell-based cancer immunotherapy. J Nat Cancer Inst. 2018;110(7):777–786. doi: 10.1093/jnci/djx257 29267866

12. Kitai Y, Kawasaki T, Sueyoshi T, Kobiyama K, Ishii KJ, Zou J, et al. DNA-containing exosomes derived from cancer cells treated with topotecan activate a STING-dependent pathway and reinforce antitumor immunity. J Immunol. 2017. 198(4):1649–1659. doi: 10.4049/jimmunol.1601694 28069806

13. Menon S, Shin S, Dy G. Advances in cancer immunotherapy in solid tumors. Cancers. 2016;8(12):106.

14. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252–264. doi: 10.1038/nrc3239 22437870

15. Wolchok JD. PD-1 blockers. Cell. 2015;162(5):937. doi: 10.1016/j.cell.2015.07.045 26317459

16. Swart M, Verbrugge I, Beltman JB. Combination approaches with immune-checkpoint blockade in cancer therapy. Front Oncol. 2016;6:233–249. doi: 10.3389/fonc.2016.00233 27847783

17. Peng J, Hamanishi J, Matsumura N, Abiko K, Murat K, Baba T, et al. Chemotherapy induces programmed cell death-ligand 1 overexpression via the nuclear factor-κB to foster an immunosuppressive tumor microenvironment in ovarian cancer. Cancer Res. 2015;75(23):5034–5045. doi: 10.1158/0008-5472.CAN-14-3098 26573793

18. Cook AM, Lesterhuis WJ, Nowak AK, Lake RA. Chemotherapy and immunotherapy: mapping the road ahead. Curr Opin Immunol. 2016;39:23–29. doi: 10.1016/j.coi.2015.12.003 26724433

19. Iwata TN, Ishii C, Ishida S, Ogitani Y, Wada T, Agatsuma T. A HER2-targeting antibody–drug conjugate, trastuzumab deruxtecan (DS-8201a), enhances antitumor immunity in a mouse model. Molecul Cancer Therapeut. 2018;17(7):1494–1503.

20. Nakada T, Masuda T, Naito H, Yoshida M, Ashida S, Morita K, et al. Novel antibody drug conjugates containing exatecan derivative-based cytotoxic payloads. Bioorg Med Chem Lett. 2016;26(6):1542–1545. doi: 10.1016/j.bmcl.2016.02.020 26898815

21. Gabrysiak M, Wachowska M, Barankiewicz J, Pilch Z, Ratajska A, Skrzypek EWA, et al. Low dose of GRP78-targeting subtilase cytotoxin improves the efficacy of photodynamic therapy in vivo. Oncol Rep. 2016;35(6):3151–3158. doi: 10.3892/or.2016.4723 27035643

22. Penichet ML, Challita PM, Shin SU, Sampogna SL, Rosenblatt JD, Morrison SL. In vivo properties of three human HER2/neu-expressing murine cell lines in immunocompetent mice. Lab Anim Sci. 1999;49(2):179–188. 10331548

23. Zhao L, Tong Q, Qian W, Li B, Zhang D, Fu T, et al. Eradication of non-Hodgkin lymphoma through the induction of tumor-specific T-cell immunity by CD20-Flex BiFP. Blood. 2013;122(26):4230–4236. doi: 10.1182/blood-2013-04-496554 24178967

24. Scheuer W, Friess T, Burtscher H, Bossenmaier B, Endl J, Hasmann M. Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res. 2009;69(24):9330–9336. doi: 10.1158/0008-5472.CAN-08-4597 19934333

25. Gibney GT, Weiner LM, Atkins MB. Predictive biomarkers for checkpoint inhibitor-based immunotherapy. The Lancet Oncology. 2016;17(12):e542–e51. doi: 10.1016/S1470-2045(16)30406-5 27924752

26. Wolchok JD, Hodi FS, Weber JS, Allison JP, Urba WJ, Robert C, et al. Development of ipilimumab: a novel immunotherapeutic approach for the treatment of advanced melanoma. Ann NY Acad Sci. 2013;1291(1):1–13.

27. Sharma P, Allison James P. Immune checkpoint targeting in cancer therapy: Toward combination strategies with curative potential. Cell. 2015;161(2):205–214. doi: 10.1016/j.cell.2015.03.030 25860605

28. Andersen MH, Schrama D, thor Straten P, Becker JC. Cytotoxic T Cells. Journal of Investigative Dermatology. 2006;126:32–41. doi: 10.1038/sj.jid.5700001 16417215

29. Mok S, Duffy CR, Allison JP. J Immunol. 2018: 200 (1 Supplement) 122.2

30. Seidel JA, Otsuka A, Kabashima K. Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations. Frontiers in oncology. 2018;8:86. doi: 10.3389/fonc.2018.00086 29644214

31. OPDIVO (Nivolumab) label [revised 2018 Nov; cited 2019 Feb 1]. Available from: https://packageinserts.bms.com/pi/pi_opdivo.pdf. 2018.


Článek vyšel v časopise

PLOS One


2019 Číslo 10

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