In less than a year ago, Science magazine identified Cancer Immunotherapy as the Breakthrough of the Year. In this short editorial, Dr Couzin-Frankel discusses some of the key developments in Cancer Immunotherapeutics, including the discovery and development of ipilumumab (anti-CTLA-4), nivolomab (anti- PD-1). MSKCC has been a part of the development of both agents through leaders including Lloyd Old, James Allison, and Jedd Wolchok. Dr. Couzin-Frankel also mentions the advent of Chimeric Antigen Receptor (CAR) T cell therapy and refers to MSKCC's report of anti-leukemia therapy in 2013 American Society of Hematology, led by our investigators Renier Brentjens, Michel Sadelain and others. In the next issue of Science, another article reviewed Emerging Principles for the Therapeutic Exploitation of Glycosylation. David Spriggs, Sam Danishefsky, and Jerry Ravetch have been part of the glycosylated protein field for several years, contributing to vaccine development and antibody Fc functional studies. The program brings these fields and investigators together to examine how immunotherapy can change the cure rates and survival in ovarian cancer. The overall Objective of the program will be: to increase the knowledge about the interactions between the host immune system and High Grade Serous Ovarian Cancer. We expect to translate that knowledge into improved treatments and longer symptom free survival for women with ovarian cancer. The program will include 4 projects: 1) MUC16 glycobiology; Personalized Vaccine Therapy in ovarian cancer; Modified T-cell Therapy of Ovarian Cancer; and Fc Modification of anti-MUC16 ectodomain antibodies to enhance efficacy.
Cancer Immunotherapy has been identified as the scientific breakthrough of 2013 by Science Magazine. This proposal contains four tightly linked projects addressing Ovarian Cancer Immunotherapeutics. The projects range rom direct antibody imaging and therapy with MUC16/CA125 antibodies to personalized vaccine therapy, immune checkpoint inhibitors and treatment with specially modified patient T cells. The overall goal of the project is to improve the cure rate and the symptom free survival of women with advanced ovarian cancer.
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| Knorr, David A; Dahan, Rony; Ravetch, Jeffrey V (2018) Toxicity of an Fc-engineered anti-CD40 antibody is abrogated by intratumoral injection and results in durable antitumor immunity. Proc Natl Acad Sci U S A 115:11048-11053 |
| Cornetta, Kenneth; Duffy, Lisa; Feldman, Steven A et al. (2018) Screening Clinical Cell Products for Replication Competent Retrovirus: The National Gene Vector Biorepository Experience. Mol Ther Methods Clin Dev 10:371-378 |
| Rafiq, Sarwish; Yeku, Oladapo O; Jackson, Hollie J et al. (2018) Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo. Nat Biotechnol 36:847-856 |
| Bournazos, Stylianos; Ravetch, Jeffrey V (2017) Fc? Receptor Function and the Design of Vaccination Strategies. Immunity 47:224-233 |
| Hectors, Stefanie J; Wagner, Mathilde; Bane, Octavia et al. (2017) Quantification of hepatocellular carcinoma heterogeneity with multiparametric magnetic resonance imaging. Sci Rep 7:2452 |
| Yeku, Oladapo; Li, Xinghuo; Brentjens, Renier J (2017) Adoptive T-Cell Therapy for Solid Tumors. Am Soc Clin Oncol Educ Book 37:193-204 |
| Szender, J Brian; Papanicolau-Sengos, Antonios; Eng, Kevin H et al. (2017) NY-ESO-1 expression predicts an aggressive phenotype of ovarian cancer. Gynecol Oncol 145:420-425 |
| Rao, Thapi Dharma; Fernández-Tejada, Alberto; Axelrod, Abram et al. (2017) Antibodies Against Specific MUC16 Glycosylation Sites Inhibit Ovarian Cancer Growth. ACS Chem Biol 12:2085-2096 |
| Bournazos, Stylianos; Wang, Taia T; Dahan, Rony et al. (2017) Signaling by Antibodies: Recent Progress. Annu Rev Immunol 35:285-311 |
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