The Latest Results from a Trial of Chimeric Antigen Receptor Immunotherapy to Treat Cancer

Immunotherapies will clearly make up a large fraction of the coming generation of targeted cancer therapies, but the state of progress is very uneven at this stage, and therapies will still be specific to types and subtypes of cancer - the primary reason why cancer research is so expensive and slow. The use of chimeric antigen receptors is one of the more promising approaches within this class of therapy, not only because it is demonstrating considerable success in initial trials, but also because it can in principle be applied to numerous types of cancer with comparatively little additional work. Here, researchers present initial results from a recent trial:

Twenty-seven of 29 patients with an advanced type of leukemia that had proved resistant to multiple other forms of therapy went into remission after their T cells were genetically engineered to fight their cancers. The immune system is well-known for its remarkable ability to locate, recognize and attack invaders like the common cold. However, the immune system is not always able to eliminate cancer cells when they form. And once malignant tumors develop, they can use a variety of evasion tactics to outwit the immune system. This experimental therapy is designed to overcome some of these challenges, harnessing the power of the immune system to fight cancers by genetically engineering patients' T cells with a synthetic receptor molecule called a CAR (for chimeric antigen receptor) that empowers the T cells to recognize and kill cancer cells that bear a specific marker, called CD19.

This trial was designed to evaluate the safety of administering the engineered cells and to lay the groundwork for future improvements. It enrolled only adult patients with advanced disease that had relapsed or would not respond to other therapies. This paper includes data from 30 participants with B-cell acute lymphoblastic leukemia who received the cells. After patients' T cells were extracted from their bodies, a specialized virus delivered the DNA instructions for making the CAR into the cells. Then, the cells were multiplied to the billions in the lab. After chemotherapy, the now-reengineered cells were infused back into the patients they came from about two weeks after they were first extracted. This study is the first CAR T-cell trial to infuse patients with an even mixture of two types of T cells (helper and killer cells, which work together to kill cancer). With the assurance that each patient gets the same mixture of cells, the researchers were able to come to conclusions about the effects of administering different doses of cells.

In 27 of 29 participants whose responses were evaluated a few weeks after the infusion, a high-sensitivity test could detect no trace of their cancer in their bone marrow. The CAR T cells eliminated cancers anywhere in the body they appeared. Of the two participants who did not go into complete remission, one eventually reenrolled in the trial and went into complete remission after receiving a higher dose of cells. Not all patients stayed in complete remission: some relapsed and were treated again with CAR T cells, and two relapsed with leukemias that were immune to the CAR T cells. It is too early to know what the long-term outcomes of the cell therapy are. "It sounds fantastic to say that we get over 90 percent remissions, but there's so much more work to do make sure they're durable remissions, to work out who's going to benefit the most, and extend this work to other diseases."

Link: http://www.eurekalert.org/pub_releases/2016-04/fhcr-s9p042716.php

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