Our immune systems fight colds and infections, what about cancer?

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Photo Credit: Mass General Cancer Center

Clinical Immunotherapy is undergoing a renaissance, with recent rapid-fire US Food and Drug Association (FDA) approval of numerous immunotherapies across several different types of cancer, including malignant melanoma, non-small cell squamous lung cancer, prostate cancer, and acute lymphocytic leukemia. This new approach to cancer treatment has begun to transform the lives of patients by unleashing the power of a their own immune system to fight their disease.

Although the immune system clearly responds to tumor cells, the fact that so many individuals die of cancer each year suggests that the immune response to tumor cells in ineffective.  The goal of the cancer immunotherapist is to understand the molecular and cellular mechanisms by which the immune system attacks tumors, and by which cancer is able to escape the immune system, and then to therapeutically intervene at critical points to promote anti-tumor responses.

Researchers at the Massachusetts General Hospital (MGH) and the Broad Institute are discovering the intricacies of how the immune system works to kill cancer. “At the MGH, we use samples of actual patient’s tumors to understand how the immune system does, or does not fight the cancer, and why,” said Nir Hacohen, PhD, Director of the MGH Center for Cancer Immunotherapy. “Our goal is to understand how immune responses against tumors are initiated, maintained and evaded, with the hope of improving the ability of the immune system to eradicate cancer. Our center laboratories — including those of Marcela Maus, Mark Cobbold and Shawn Demehri at MGH — are developing new ways to target cancers in patients.”

How Immunotherapeutics Work

Not all cancer immunotherapies work in the same way. As the understanding of the immune system and how it interacts with cancer cells increases, we can expect to see novel immunotherapies and new ways to use existing ones. The way in which different immunotherapeutics work to benefit a patient varies, with several possible mechanisms (only a few are shown here):

  1. MARK THE TUMOR. These were the first widespread immunotherapies; an example is the HER2 antibody, Herceptin, and others like it, which flag a tumor with a specific antibody that then triggers tumor elimination.
  2. RELEASE NATURAL BRAKES: These antibody-based therapies release natural processes that block the existing cancer-fighting immune response. These therapies work across many tumor types and have revolutionized cancer treatment in the past few years, providing durable cures in some patients.
  3. DIRECT TRANSFER OF T CELLS. In this approach, tumor-homing T cells are generated and transferred into patients to kill tumors. This has shown some dramatic successes for blood leukemias in recent years and has much potential but much work left to generalize the approach.
  4. INDUCE IMMUNITY: These therapeutics include vaccines that trigger specific immune responses against the tumor. These are still under development but provide hope for safer and highly specific therapies.

Given that some patients have remarkable and durable responses following immunotherapy, this form of cancer treatment holds incredible promise for the future, with durable cures for some patients.  Most of the progress is very recent, and most experimental cancer immunotherapies, are still in clinical development and have, therefore, not yet been approved by the FDA.

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