Immune to Cancer: The CRI Blog

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Genetically Engineered CAR T Cells Prove Highly Effective Against Blood Cancers

Adoptive cell therapy

This past Sunday, at the American Association for the Advancement of Science’s (AAAS) annual meeting in Washington, D.C., researchers revealed the most promising results yet regarding a “revolutionary” cancer treatment. The treatment—known as chimeric antigen receptor (CAR) T cell therapy—belongs to a relatively new class of cancer treatments called immunotherapy, which empowers a patient’s immune system to eliminate cancer.

Previously, another type of CAR T cell therapy enabled young Emily Whitehead—whose story you can read here—to conquer her life-threatening leukemia. Now, a new version has shown amazing effectiveness in patients with other blood cancers.

In a new study led by Stanley Riddell, MD—a member of the Cancer Research Institute’s (CRI) Scientific Advisory Council and former CRI-funded investigator—93% of patients with acute lymphoblastic leukemia (ALL) achieved remission after receiving treatment, while 63% of non-Hodgkin lymphoma patients also saw improved outcomes. Many of these patients had tumors that were resistant to chemotherapy.

Cancer cells often employ evasive tactics to avoid destruction via immune T cells. To overcome this, CAR T cell immunotherapy works by harvesting a patient’s own T cells, genetically modifying them to improve their ability to identify and destroy harmful cancer cells, and then putting them back in the patient. This video below provides great visuals on how the technology works.


VIDEO


In addition to the improved cancer-killing ability of these T cells, they can also act as a “living drug” that provides patients with long-term defense. According to Chiara Bonini, PhD, who conducts research at the San Raffaele Scientific Institute in Milan, Italy, these engineered T cells can persist in patients for at least 14 years, and may resume their anti-cancer activity if a tumor comes back.

Dr. Riddell’s study highlighted the ability of these T cells to recognize and eliminate blood cancer cells, while Dr. Bonini’s research revealed the long-term persistence of these cells. Both of these facts bode well for the potential of CAR T cell therapy; however, one major hurdle of this approach stems from the difficulty of quickly obtaining enough T cells—in some cases millions or billions—for the treatment.

To that end, the work of Dirk Busch, M.D. may enable future treatments to circumvent that requirement. Using mice that lacked T cells, Dr. Busch and his team at the Technical University of Munich showed that a single genetically engineered T cell proved sufficient to revitalize the mice’s adaptive immune systems, and enabled them to successfully fend off infections. While cancer differs from an infection, overcoming both depends on a competent adaptive immune response.

Taken together, these results may give the impression that it’s only a matter of time before this treatment provides the answer to cancer. Unfortunately, these treatments are far from perfect, as evidenced by the fact that two patients in Dr. Riddell’s study died from overactive immune responses. Researchers around the world are looking for ways refine the treatments and minimize or prevent collateral damage.

While 2015 was “a truly special year for immunotherapy,” as evidenced by its use in half of all current clinical trials for cancer, much work remains to be done to optimize these treatments. These opportunities offer great promise as well as crucial insight into immunotherapy, and will hopefully enable scientists to develop effective strategies for all cancer patients.

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