Journal
CURRENT OPINION IN IMMUNOLOGY
Volume 33, Issue -, Pages 23-35Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/j.coi.2015.01.006
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Funding
- National Institutes of Health (NIH) [P01 CA168585, 2U54 CA151819, R01CA170689, P01 CA132681]
- Stand Up to Cancer-Cancer Research Institute (SU2C-CRI) [SUC2CR-AACR-DT10]
- Melanoma Research Foundation
- Dr. Robert Vigen Memorial Fund
- Ressler Family Foundation
- Wesley Coyle Memorial Fund
- Oncology training grant [5T32CA009297-30]
- Dermatology training grant [5T32AR058921-05]
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Unleashing the immune system to fight cancer has become one of the main treatment modalities since the anti-CTLA-4 antibody, ipilimumab was approved for patients with advanced melanoma in 2011. Pembrolizumab and nivolumab, two anti-PD-1 antibodies recently approved for the treatment of patients with metastatic melanoma, are being actively investigated for the treatment of multiple caners including lung, breast, bladder and renal cancers along with other anti-PD-1/L1 antibodies. Early results of combining of anti-CTLA-4 antibody and anti-PD-1 antibody treatment for advanced melanoma patients are showing impressive response rates with manageable toxicity profiles. There are several other checkpoint molecules that are likely potential inhibitory targets. The outcome of blocking some of these negative immune regulators, such as LAG-3 or TIM-3, is being pursued in the clinic or about to enter clinical development. Blockade of these molecules is demonstrating promising preclinical activity alone or when combined with anti-PD-1/L1. Future studies will define bio-markers of these therapies and how to target them alone or in combination with other immunotherapies, chemotherapy, radiotherapy and small molecule inhibitors.
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