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Unleashing the Immune System to Cure Cancer

January 8, 2019

The answer is within you. It sounds like conventional advice on happiness, but it’s being applied to cancer therapy.

Traditionally, cancer therapy has relied on indiscriminate force to attack and destroy malignant cells. A turning point came recently with the advent of immunotherapy as a strategy to harness the immune system’s power to recognize and kill cancer cells with great precision.

Our immune system is a finely tuned machine evolved to track down and destroy pathogens, virus-infected cells and malignant cells. Unfortunately, because cancer arises from our own tissues, cancer cells can hide from the immune system and go undetected. Additionally, checks and balances are in place to keep immunity under control and prevent reactions against ourselves, and cancer uses these mechanisms to its advantage, developing ways to circumvent and inhibit immunity.

The immunotherapy approach consists of helping our immune system recognize cancer more effectively and enhancing our natural antitumor response. Several avenues have been explored and have led to different approaches that are changing the way advanced-stage patients are treated and significantly impacting prognosis.

Checkpoint Inhibitors

Building on discoveries from the past two decades, scientists have created molecules called checkpoint inhibitors that release the natural brakes on T cells and other effector immune cells, unleashing their full force against cancer. The revolutionary impact of this research was recognized when the 2018 Nobel Prize in medicine was awarded to two scientists that pioneered this field: James P. Allison, Ph.D, and Tasuku Honjo, M.D., Ph.D.

Since 2011, seven immune checkpoint inhibitors have been approved by the FDA for use by patients* and have brought long-lasting remission and longer survival to advanced-stage cancer patients, particularly with melanoma, lung and bladder cancer. Although some patients have been in remission for years thanks to these therapies, this approach only works for a fraction of patients and even those who initially show a response can develop resistance later.

Ongoing research efforts are investigating markers and mechanisms of innate and acquired resistance and developing new immune modulatory molecules and combination therapies to provide extended disease control.

Cell Therapy

CAR-T cell therapy, also called adoptive cell immunotherapy, consists of reprogramming a patient’s own immune cells to make them more effective at killing cancer cells. T cells are collected from the patient and genetically engineered to more effectively recognize a molecule present on cancer cells. Then, they are multiplied in large numbers in the laboratory and finally injected as a transfusion into the patient, where they will continue to divide and fight cancer.

This type of treatment is effective for certain blood cancers such as leukemia and lymphoma, although not in all patients. The first CAR-T cell therapy received FDA approval in 2017. To reduce the possibility of resistance, researchers are devising CAR-T cells that target more than one cancer molecule. They are also working to find suitable targets to make this approach effective for solid tumors.

Cancer Vaccines

Vaccines that protect people from viral infections associated with cancer have been shown effective in preventing disease. This is the case in human papillomavirus (HPV) vaccines, which prevent cervical cancer and other cancer types associated with this virus; and the hepatitis B vaccine that protects from liver cancer due to hepatitis B infection.

Researchers have applied similar tools to develop therapeutic vaccines to treat cancers that are not caused by viral infection. In this case, vaccines are used to strengthen the body’s natural defenses against cancer. Therapeutic cancer vaccines are designed to introduce antigens that stimulate immune responses against similar molecules present on existing cancer cells in the body. As a result, the immune system will use the army of cells and antibodies produced against the vaccine to attack the cancer.

Other immunotherapy approaches under development are oncolytic viruses that infect and kill tumor cells and cause the release of cancer-derived material that alerts the immune system; and bispecific monoclonal antibodies, which simultaneously bind molecules present on cancer cells and immune cells, thus bringing them together and directing T-cell toxicity to malignant cells.

Immunotherapy Research at Wistar

Scientists at Wistar combine their expertise in cancer, immunology and vaccine development by taking a multidisciplinary approach to cancer immunotherapy research. Their work spans from seminal investigations in tumor immunology to characterize the role of different immune cell populations in cancer, to development of new immunotherapeutic approaches.

These include novel adoptive T-cell therapies for solid tumors, cancer vaccines, and new generation immunotherapy platforms based on synthetic DNA such as synthetic DNA vaccines and DNA-encoded monoclonal antibodies.

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