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, according to a report (“CD19 CAR–T Cells of Defined CD4+:CD8+ Composition in Adult B Cell ALL Patients”) in the Journal of Clinical Investigation.

This experimental therapy is designed to harness 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. The paper includes data from 30 participants with B-cell acute lymphoblastic leukemia who received the cells in Seattle through the Fred Hutchinson/University of Washington Cancer Consortium. 

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 2 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, the researchers said.

The researchers also learned how to revise their strategy to lower the risks of serious side effects and prevent rejection of the engineered cells. They also gathered data that may help them predict serious side effects in the future.

“Patients who come onto the trial have really limited options for treatment. They have refractory acute leukemia. So the fact that we're getting so many into remission is giving these people a way forward,” said study leader Cameron Turtle, Ph.D. “In early-phase trials, you're continually learning. You don't expect results like these from early-phase trials. That's why these response rates are so extraordinary,” added senior author David Maloney, M.D., Ph.D.

“This is just the beginning,” noted Dr. Turtle. “It sounds fantastic to say that we get over 90% 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.”

The paper includes the largest number of participants of any other published study using CD19 CAR T cells against this particular type of cancer. It is also the first to infuse patients with a defined ratio of killer and helper T cells. This well-controlled method allowed the authors to provide the first clear evidence of the relationships between the doses of cells participants received and their outcomes after infusion.

As an early-phase trial, this study was not designed to provide definitive evidence of the therapy's effectiveness against cancer. The study also had a small number of participants, but the trial continues to enroll and will publish results from larger number of participants in the future.

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