PT-112 induces immunogenic cell death and synergizes with immune checkpoint blockers in mouse tumor models

References

• Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350:2343–10. doi:10.1056/NEJMoa032709.
   PubMed Web of Science ®Google Scholar
• Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004;350:351–360.
   PubMed Web of Science ®Google Scholar
• International Collaborative Ovarian Neoplasm G. Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet. 2002;360:505–515. doi:10.1016/S0140-6736(02)09738-6.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Senovilla L, Vitale I, Michels J, Martins I, Kepp O, Castedo M, Kroemer G. Molecular mechanisms of cisplatin resistance. Oncogene. 2012;31:1869–1883. doi:10.1038/onc.2011.384.
   PubMed Web of Science ®Google Scholar
• Guminski AD, Harnett PR, deFazio A. Scientists and clinicians test their metal-back to the future with platinum compounds. Lancet Oncol. 2002;3:312–318. doi:10.1016/S1470-2045(02)00733-7.
   PubMed Web of Science ®Google Scholar
• Bose RN, Maurmann L, Mishur RJ, Yasui L, Gupta S, Grayburn WS, Hofstetter H, Salley T. Non-DNA-binding platinum anticancer agents: cytotoxic activities of platinum-phosphato complexes towards human ovarian cancer cells. Proc Natl Acad Sci U S A. 2008;105:18314–18319. doi:10.1073/pnas.0803094105.
   PubMed Web of Science ®Google Scholar
• Ames T, Slusher B, Wozniak K, Takase Y, Shimizu H, Nishibata-Kobayashi K, Kanada-Sonobe RM, Kerns W, Fong KL, Pourquier P, et al. Findings across pre-clinical models in the development of PT-112, a novel investigational platinum-pyrophosphate anti-cancer agent. Eur J Cancer. 2016;69:S153. doi:10.1016/S0959-8049(16)33054-4.
   Web of Science ®Google Scholar
• Yamazaki T, Ames TD, Galluzzi L. Abstract B199: potent induction of immunogenic cell death by PT-112. Cancer Immunol Res. 2019;7:B199–B.
   Web of Science ®Google Scholar
• Corte-Rodriguez M, Espina M, Sierra LM, Blanco E, Ames T, Montes-Bayon M, Sanz-Medel A. Quantitative evaluation of cellular uptake, DNA incorporation and adduct formation in cisplatin sensitive and resistant cell lines: comparison of different Pt-containing drugs. Biochem Pharmacol. 2015;98:69–77. doi:10.1016/j.bcp.2015.08.112.
   PubMed Web of Science ®Google Scholar
• Bose RN, Moghaddas S, Belkacemi L, Tripathi S, Adams NR, Majmudar P, McCall K, Dezvareh H, Nislow C. Absence of activation of DNA repair genes and excellent efficacy of phosphaplatins against human ovarian cancers: implications to treat resistant cancers. J Med Chem. 2015;58:8387–8401. doi:10.1021/acs.jmedchem.5b00732.
   PubMed Web of Science ®Google Scholar
• Karp DD, Camidge DR, Bryce AH, Jimeno J, Infante JR. A phase I study of PT-112 in advanced solid tumors. J Clin Oncol. 2017;35:2519. doi:10.1200/JCO.2017.35.15_suppl.2519.
   Google Scholar
• Karp DD, Camidge DR, Infante JR, Ames TD, Jimeno JM, Bryce AH. PT-112: A well-tolerated novel immunogenic cell death (ICD) inducer with activity in advanced solid tumors. Ann Oncol. 2018;29. doi:10.1093/annonc/mdy279.424.
   PubMed Web of Science ®Google Scholar
• Ames TD, Sharik ME, Rather GM, Hochart G, Bonnel D, Linehan S, Stauber J, Wing RA, Jimeno JJ, Medina D, et al. Translational research of PT-112, a clinical agent in advanced phase i development: evident bone tropism, synergy in vitro with bortezomib and lenalidomide, and potent efficacy in the Vk*MYC mouse model of multiple myeloma. Blood. 2017;130:1797.
   Web of Science ®Google Scholar
• Bryce AH, Dronca RS, Costello BA, Infante JR, Ames TD, Jimeno JM, Karp DD. PT-112 in advanced metastatic castrate-resistant prostate cancer (mCRPC), as monotherapy or in combination with PD-L1 inhibitor avelumab: findings from two phase I studies. J Clin Oncol. 2020;38.
   Google Scholar
• Galluzzi L, Chan TA, Kroemer G, Wolchok JD, Lopez-Soto A. The hallmarks of successful anticancer immunotherapy. Sci Transl Med. 2018;10:eaat7807. doi:10.1126/scitranslmed.aat7807.
   PubMed Web of Science ®Google Scholar
• Tang J, Yu JX, Hubbard-Lucey VM, Neftelinov ST, Hodge JP, Lin Y. Trial watch: the clinical trial landscape for PD1/PDL1 immune checkpoint inhibitors. Nat Rev Drug Discov. 2018;17:854–855. doi:10.1038/nrd.2018.210.
   PubMed Web of Science ®Google Scholar
• Taghizadeh H, Marhold M, Tomasich E, Udovica S, Merchant A, Krainer M. Immune checkpoint inhibitors in mCRPC - rationales, challenges and perspectives. Oncoimmunology. 2019;8:e1644109. doi:10.1080/2162402X.2019.1644109.
   PubMed Web of Science ®Google Scholar
• Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 2015;161:205–214. doi:10.1016/j.cell.2015.03.030.
   PubMed Web of Science ®Google Scholar
• Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015;348:56–61. doi:10.1126/science.aaa8172.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, Alnemri ES, Altucci L, Amelio I, Andrews DW, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 2018;25:486–541.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Buque A, Kepp O, Zitvogel L, Kroemer G. Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol. 2017;17:97–111. doi:10.1038/nri.2016.107.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Yamazaki T, Kroemer G. Linking cellular stress responses to systemic homeostasis. Nat Rev Mol Cell Biol. 2018;19:731–745. doi:10.1038/s41580-018-0068-0.
   PubMed Web of Science ®Google Scholar
• Tesniere A, Schlemmer F, Boige V, Kepp O, Martins I, Ghiringhelli F, Aymeric L, Michaud M, Apetoh L, Barault L, et al. Immunogenic death of colon cancer cells treated with oxaliplatin. Oncogene. 2010;29:482–491. doi:10.1038/onc.2009.356.
   PubMed Web of Science ®Google Scholar
• Martins I, Kepp O, Schlemmer F, Adjemian S, Tailler M, Shen S, Michaud M, Menger L, Gdoura A, Tajeddine N, et al. Restoration of the immunogenicity of cisplatin-induced cancer cell death by endoplasmic reticulum stress. Oncogene. 2011;30:1147–1158. doi:10.1038/onc.2010.500.
   PubMed Web of Science ®Google Scholar
• Tatsuno K, Yamazaki T, Hanlon D, Han P, Robinson E, Sobolev O, Yurter A, Rivera-Molina F, Arshad N, Edelson RL, et al. Extracorporeal photochemotherapy induces bona fide immunogenic cell death. Cell Death Dis. 2019;10:578. doi:10.1038/s41419-019-1819-3.
   PubMed Web of Science ®Google Scholar
• Park SJ, Ye W, Xiao R, Silvin C, Padget M, Hodge JW, Van Waes C, Schmitt NC. Cisplatin and oxaliplatin induce similar immunogenic changes in preclinical models of head and neck cancer. Oral Oncol. 2019;95:127–135. doi:10.1016/j.oraloncology.2019.06.016.
   PubMed Web of Science ®Google Scholar
• Humeau J, Levesque S, Kroemer G, Pol JG. Gold standard assessment of immunogenic cell death in oncological mouse models. Methods Mol Biol. 2019;1884:297–315.
   PubMedGoogle Scholar
• Yamazaki T, Martinez AB, Rybstein M, Chen J, Sato A, Galluzzi L. Methods to detect immunogenic cell death in vivo. Methods Mol Biol. 2020;2055:433–452.
   PubMedGoogle Scholar
• Hoffmann J, Vitale I, Buchmann B, Galluzzi L, Schwede W, Senovilla L, Skuballa W, Vivet S, Lichtner RB, Vicencio JM, et al. Improved cellular pharmacokinetics and pharmacodynamics underlie the wide anticancer activity of sagopilone. Cancer Res. 2008;68:5301–5308. doi:10.1158/0008-5472.CAN-08-0237.
   PubMed Web of Science ®Google Scholar
• Kepp O, Senovilla L, Vitale I, Vacchelli E, Adjemian S, Agostinis P, Apetoh L, Aranda F, Barnaba V, Bloy N, et al. Consensus guidelines for the detection of immunogenic cell death. Oncoimmunology. 2014;3:e955691. doi:10.4161/21624011.2014.955691.
   PubMed Web of Science ®Google Scholar
• Fucikova J, Rakova J, Hensler M, Kasikova L, Belicova L, Hladikova K, Truxova I, Skapa P, Laco J, Pecen L, et al. TIM-3 Dictates Functional Orientation of the Immune Infiltrate in Ovarian Cancer. Clin Cancer Res. 2019;25:4820–4831. doi:10.1158/1078-0432.CCR-18-4175.
   PubMed Web of Science ®Google Scholar
• Buque A, Galluzzi L. Modeling tumor immunology and immunotherapy in mice. Trends Cancer. 2018;4:599–601. doi:10.1016/j.trecan.2018.07.003.
   PubMed Web of Science ®Google Scholar
• Garg AD, More S, Rufo N, Mece O, Sassano ML, Agostinis P, Zitvogel L, Kroemer G, Galluzzi L. Trial watch: immunogenic cell death induction by anticancer chemotherapeutics. Oncoimmunology. 2017;6:e1386829. doi:10.1080/2162402X.2017.1386829.
   PubMed Web of Science ®Google Scholar
• Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini J-L, Castedo M, Mignot G, Panaretakis T, Casares N, et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med. 2007;13:54–61. doi:10.1038/nm1523.
   PubMed Web of Science ®Google Scholar
• Grabosch S, Bulatovic M, Zeng F, Ma T, Zhang L, Ross M, Brozick J, Fang Y, Tseng G, Kim E, et al. Cisplatin-induced immune modulation in ovarian cancer mouse models with distinct inflammation profiles. Oncogene. 2019;38:2380–2393. doi:10.1038/s41388-018-0581-9.
   PubMed Web of Science ®Google Scholar
• Menger L, Vacchelli E, Adjemian S, Martins I, Ma Y, Shen S, Yamazaki T, Sukkurwala AQ, Michaud M, Mignot G, et al. Cardiac glycosides exert anticancer effects by inducing immunogenic cell death. Sci Transl Med. 2012;4:143ra99. doi:10.1126/scitranslmed.3003807.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Ruiz ME, Buque A, Hensler M, Chen J, Bloy N, Petroni G, Sato A, Yamazaki T, Fucikova J, Galluzzi L, et al. Apoptotic caspases inhibit abscopal responses to radiation and identify a new prognostic biomarker for breast cancer patients. Oncoimmunology. 2019;8:e1655964. doi:10.1080/2162402X.2019.1655964.
   PubMed Web of Science ®Google Scholar
• Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res. 2006;12:6243s–9s. doi:10.1158/1078-0432.CCR-06-0931.
   PubMed Web of Science ®Google Scholar
• Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2001;27:165–176. doi:10.1053/ctrv.2000.0210.
   PubMed Web of Science ®Google Scholar
• Langer CJ, Gadgeel SM, Borghaei H, Papadimitrakopoulou VA, Patnaik A, Powell SF, Gentzler RD, Martins RG, Stevenson JP, Jalal SI, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016;17:1497–1508. doi:10.1016/S1470-2045(16)30498-3.
   PubMed Web of Science ®Google Scholar
• Morse MA, Hochster H, Benson A. Perspectives on treatment of metastatic colorectal cancer with immune checkpoint inhibitor therapy. Oncologist. 2019. doi:10.1634/theoncologist.2019-0176.
   Google Scholar
• Rugo HS, Delord JP, Im SA, Ott PA, Piha-Paul SA, Bedard PL, Sachdev J, Tourneau CL, van Brummelen EMJ, Varga A, et al. Safety and antitumor activity of pembrolizumab in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. Clin Cancer Res. 2018;24:2804–2811. doi:10.1158/1078-0432.CCR-17-3452.
   PubMed Web of Science ®Google Scholar
• Tucker MD, Zhu J, Marin D, Gupta RT, Gupta S, Berry WR, Ramalingam S, Zhang T, Harrison M, Wu Y, et al. Pembrolizumab in men with heavily treated metastatic castrate-resistant prostate cancer. Cancer Med. 2019;8:4644–4655. doi:10.1002/cam4.v8.10.
   PubMed Web of Science ®Google Scholar
• Aroldi F, Zaniboni A. Immunotherapy for pancreatic cancer: present and future. Immunotherapy. 2017;9:607–616. doi:10.2217/imt-2016-0142.
   PubMed Web of Science ®Google Scholar
• Marino S, Petrusca DN, Roodman GD. Therapeutic targets in myeloma bone disease. Br J Pharmacol. 2019. doi:10.1111/bph.14889.
   Web of Science ®Google Scholar