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Releasing the Brakes on Cancer Immunotherapy

The following is a summary of an article written by Antoni Ribas, MD, PhD, that was published in the October, 15, 2015 issue of the New England Journal of Medicine.

Antoni Ribas, MD, PhD, Director of UCLA's Jonsson Comprehensive Cancer Center's Tumor Immunology Program Area, recently published a "Perspective" article in the October 15, 2015 issue of The New England Journal of Medicine. Ribas's article, entitled "Releasing the Brakes on Cancer Immunotherapy," discusses the evolution of the potential of the human body's immune system in fighting cancer.

Back in the 1980s and 1990s, the immunologist James P. Allison* had hypothesized that the immune system possessed the ability to fight cancer by blocking negative immune regulators, otherwise known as checkpoints. As time progressed and Allison's hypothesis transitioned to clinical experimentation, his theory came to light—his research was proving that immunotherapy could serve a critical role in the treatment of cancer.

Allison spent much of his time and early research efforts focusing on T-cell activation, outlining the structure of T-cell receptors, and understanding the ways by which the human body's immune system was activated. Further experimentation explored the checkpoint molecule CTLA-4—cytotoxic T-lymphocyte-associated protein 4—and its ability to inhibit T-cell activation. Allison would later discover that by using antibodies to block CTLA-4, an immune response could be triggered against cancer cells.

Allison's discovery, currently referred to as checkpoint-blockade immunotherapy, is considered by researchers to be one of the most promising advances in the treatment of cancer to evolve in recent years. Among the therapeutic antibodies currently on the market are ipilimumab which blocks CTLA-4 for the treatment of metastatic melanoma and pembrolizumab and nivolumab which block the molecule PD-1 for the treatment of lung carcinoma and metastatic melanoma. Several additional therapeutic antibodies are in the clinical development stages for the treatment of more than 30 different types of cancer.

While immunotherapy treatments for cancer patients hold great hope for improved survival outcomes, as with any novel treatment regimen there are accompanying risk factors. While testing the limits of the body's immune system with this type of therapy, serious autoimmune side effects may occur.

*James P. Allison is the 2015 Lasker~DeBakey Clinical Medical Research Award recipient for his groundbreaking research in immunotherapy and its resultant impact on cancer treatment.

Sources

Source

Releasing the Brakes on Cancer Immunotherapy. N Engl J Med. 2015 Oct 15;373(16):1490-2.

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