Detect. Destroy. Remember. The mantra of the immune system's relentless campaign against infectious invaders and the body's own abnormal cells finally is applying to cancer in meaningful ways.
The journal Science named cancer immunotherapy its 2013 Breakthrough of the Year, the latest recognition of the rising tide of treatments pioneered by Texan-born Jim Allison, Ph.D., chair of Immunology at The University of Texas MD Anderson Cancer Center and executive director of its Moon Shots Program immunotherapy platform.
"Immunotherapy marks an entirely different way of treating cancer—by targeting the immune system, not the tumor itself. Oncologists, a grounded-in-reality bunch, say a corner has been turned and we won't be going back," the Science story noted. It leads with Allison's discoveries and subsequent drug development.
"Jim Allison was the first to turn that corner by revealing how tumors sideline the immune system. He then developed a new class of medicine that activates an immune response against cancer, extending survival for patients with late stage-melanoma - and even curing some," MD Anderson President Ronald DePinho, M.D., said.
"His leadership continues to advance this exciting treatment and underpins the comprehensive efforts of MD Anderson's Moon Shots Program to dramatically reduce cancer deaths," DePinho added. The immunotherapy platform has enhanced and increased the institution's capabilities in expertise, technology and techniques since Allison's arrival in November of 2012.
"Science's choice of immunotherapy recognizes what this field is accomplishing right now and the prospect of deeper and broader application against many types of cancer to come," Allison said.
On Dec. 12, Allison received a Breakthrough Prize for Biosciences from the Breakthrough Foundation, The Economist's 2013 Innovations Award for Bioscience on Dec. 3, and the first AACR-CRI Lloyd J. Old Award in Cancer Immunology of the American Association for Cancer Research in April.
Immunotherapy paying off at last
For decades, researchers have strived to use the immune system to destroy cancer cells. In addition to recognizing, destroying and remembering viral and bacterial infections, the immune system routinely does the same thing to the body's own abnormal cells, the type that develops into cancer.
However, vaccines and other immune therapies developed to hit cancer were bedeviled by tumor defenses, resulting in minimal impact on the cancer if not outright treatment failure.
Allison's basic research on the biology of T cells - the supremely targeted shock troops of the immune system - revealed an important reason why. He found that a receptor on T cells acts as an "off switch" to shut down activated T cells. Designed to protect normal cells from T cell attack, tumor cells also are equipped to fire up the receptor CTLA-4 to stop a targeted immune system assault.
Allison developed an antibody to block CTLA-4 that went on to become the drug ipilimumab (Yervoy). In clinical trials against stage 4 metastatic melanoma, the drug extinguished the disease in 20 percent of patients for up to 12 years and counting, previously unheard of results for terminal melanoma. It was approved to treat advanced melanoma by the U.S. Food and Drug Administration in 2011.
MD Anderson cultivates immunotherapy
Additional immune checkpoints and experimental drugs to block them have since been developed by others. Clinical trials of these agents and ipilimumab at MD Anderson target melanoma, lymphoma, lung, breast, gastric and prostate cancers with more to come.
Combination therapies are being tested to increase the number of patients who respond to the drug. Half of patients in a small clinical trial reported in the New England Journal of Medicine responded strongly to ipilimumab combined with another drug that blocks the PD-1 checkpoint.
"The two drugs appear to have a synergistic effect, with the combination accomplishing more than either drug does alone," Allison said.
MD Anderson scientists also have developed immune therapies now in clinical trials that:
•Harvest T cells from tumors that are primed to attack but overwhelmed by cancer cell defenses. These tumor-infiltrating lymphocytes are cultivated and vastly expanded in the lab, then given back to the patient. Hwu leads this project in melanoma.
•Use gene transfer techniques to customize T cells against cancer, expanding them in the lab and infusing them back in the patient.
•Deploy new therapeutic vaccines, including ones that target breast cancer, melanoma and blood malignancies.
"MD Anderson is a center of immunotherapy excellence that will grow, improve and significantly contribute to development of more effective drugs for cancer patients," Allison said.
The University of Texas MD Anderson Cancer Center