It is now quite clear that a subset of patients with metastatic melanoma treated with CTLA-4 blocking antibodies have durable clinical benefit. The experience of our group and others leads us to several vital questions which require answers so that more patients may benefit. The preliminary data show that patients with pre-existing or induced immunity to NY-ESO-1 have a higher likelihood of clinical benefit. Validation of this observation in the large population of patients treated on a randomized trial in the adjuvant setting will further inform us of the importance of NY-ESO-1 immunity. If our initial observations are confirmed, that knowledge could lead to two impactful moves: (1) prospective identification of patients with pre-existing antibodies for up-front treatment with this and other immunotherapies and (2) incorporation of NY-ESO-1 vaccines into treatment programs for patients with no pre-existing immunity. Outside of the area of immunotherapy, this study will be the largest survey of NY-ESO-1 immunity in patients at the stage III to IV transition. The prognostic importance of sero-status in the adjuvant setting will be determined by our work. Further, the proposed analysis of patients treated with ipilimumab alone or in combination with chemotherapy will be highly significant as this and other immunotherapeutics move toward standard use. Knowledge of how chemotherapy may augment or detract from the immunologic effects of CTLA-4 blockade will inform the field concerning rational combination therapies.

Public Health Relevance

Preliminary data show that patients with pre-existing or induced immunity to NY-ESO-1 have a higher likelihood of clinical benefit. Validation of this observation in the large population of patients treated on a randomized trial in the adjuvant setting will further inform us of the importance of NY-ESO-1 immunity.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
High Impact Research and Research Infrastructure Programs (RC2)
Project #
5RC2CA148468-02
Application #
7943943
Study Section
Special Emphasis Panel (ZCA1-RPRB-J (O9))
Program Officer
Agarwal, Rajeev K
Project Start
2009-09-29
Project End
2012-08-31
Budget Start
2010-09-01
Budget End
2012-08-31
Support Year
2
Fiscal Year
2010
Total Cost
$945,556
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Kitano, Shigehisa; Postow, Michael A; Ziegler, Carly G K et al. (2014) Computational algorithm-driven evaluation of monocytic myeloid-derived suppressor cell frequency for prediction of clinical outcomes. Cancer Immunol Res 2:812-21
Yuan, Jianda; Zhou, Jun; Dong, Zhiwan et al. (2014) Pretreatment serum VEGF is associated with clinical response and overall survival in advanced melanoma patients treated with ipilimumab. Cancer Immunol Res 2:127-32
Callahan, Margaret K; Postow, Michael A; Wolchok, Jedd D (2013) Immunomodulatory therapy for melanoma: ipilimumab and beyond. Clin Dermatol 31:191-9
Ribas, Antoni; Wolchok, Jedd D (2013) Combining cancer immunotherapy and targeted therapy. Curr Opin Immunol 25:291-6
Kitano, Shigehisa; Tsuji, Takemasa; Liu, Caillian et al. (2013) Enhancement of tumor-reactive cytotoxic CD4+ T cell responses after ipilimumab treatment in four advanced melanoma patients. Cancer Immunol Res 1:235-44
Postow, Michael A; Luke, Jason J; Bluth, Mark J et al. (2013) Ipilimumab for patients with advanced mucosal melanoma. Oncologist 18:726-32
Postow, Michael A; Callahan, Margaret K; Barker, Christopher A et al. (2012) Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med 366:925-31
Lesokhin, Alexander M; Hohl, Tobias M; Kitano, Shigehisa et al. (2012) Monocytic CCR2(+) myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment. Cancer Res 72:876-86
Postow, Michael; Callahan, Margaret K; Wolchok, Jedd D (2011) Beyond cancer vaccines: a reason for future optimism with immunomodulatory therapy. Cancer J 17:372-8
Yuan, Jianda; Ginsberg, Brian; Page, David et al. (2011) CTLA-4 blockade increases antigen-specific CD8(+) T cells in prevaccinated patients with melanoma: three cases. Cancer Immunol Immunother 60:1137-46