CAR T Cells: Crafted for Myeloma Treatment

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Cancer has a 4000-year-old history. When Sydney Farber, the father of chemotherapy, accidentally discovered an anticancer compound, he must have been thrilled to a reach a cure for cancer. But little did he imagine that cancer could be so sly to keep changing its face. However, it did not take our medical fraternity too long to figure that out, and they are not giving up the chase anytime sooner. They are continuously discovering new ways to engineer and train our immune system cells to recognize and attack every new mask that a cancer cell shows up with.

Last year in April, on CureTalks we discussed a cutting edge breakthrough myeloma therapy called the CAR-T cell (Chimeric Antigen Receptor T Cell) therapy with Dr. Craig Hofmeister, Assistant Professor of Medicine at the Ohio State University Comprehensive Cancer Center. In this talk, Dr. Hofmeister enlightened us about this new research and immunotherapy in a very meticulous and simple way so as to let the layman understand what this therapy ensues.

What are CAR T cells?

T cells and B cells are essential components of our immune system. Normally T cells sport many receptors on their surface which help them recognize and attack a potential foreign invader like bacteria, fungus etc. A CAR T cell is a genetically engineered T cell that has receptors, which target potentially more than one receptor present on myeloma cells.

Why is this genetic modification of T cells needed?

Cancer is crafty. Cancer cells have the ability to create a protective layer on and around its cell surface, so that our own T cells don’t recognize these cancer cells as foreign. In order to counter-attack the cancer cell’s strategy, we need to force a T cell to put up a chimeric or synthetic T cell on its surface, through genetic modification, forcing that T cell to recognize a particular antigen or a particular protein on the cell surface of all myeloma cells.

Although still in its infancy for myeloma treatment, these CAR T cells have been used effectively in other blood cancers like ALL, CLL and aggressive lymphoma called diffuse large B cell lymphoma, which is a type of non-Hodgkin’s lymphoma, with fabulous results. Dr. Hofmeister’s team is trying to engineer CAR T cells to target a CS1 protein antigen on the surface of myeloma cells. The team works on the hypothesis that the majority of relapsed myeloma patients have CS1 on the cell surface of myeloma.

The initial tests inbred mouse models have given very assuring results to the team that hopes to “bring this to patients because in-bred mice really aren’t as reflective of a patient’s immune system and the complexity of human disease.” It takes about 2 weeks for the CAR T cells to multiply in a patient’s body, so he said, he would expect this therapy to show some response or improvement in the patients in around 2-4 weeks after the administration of this therapy.

Currently, CAR T cell trials cost an extraordinary amount per patient, somewhere near 100,000 and 500,000 dollars, just to treat a single patient. This cost covers: extracting the patient’s T cells, genetically modifying them, expanding those genetically modified cells in a sterile and supportive environment, and then infusing those cells back into the patient and monitoring the patient for side effects and for effectiveness. However, “this is the first wave and the first wave is never perfect” says Dr. Hofmeister. He assures that the scientific community is trying hard to make the treatment better, safer and most cost effective.

Dr. Hofmeister confides that it is difficult to provide a timeline when this therapy could be administered in patients practically, but tells that Ohio state, University of Pennsylvania, Dana-Farber, the NCI, National Cancer Institute, are doing these CAR T cells trials and many other trials are to open up in London, France, and other spots in the US.

At the 52nd Annual Meeting of the Drug Information Association DIA2016 held recently in Philadelphia, the US Food and Drug Administration (FDA) presented its belief in the potential benefits that these CAR T cells possess as novel immunotherapy that can be used to treat many cancers. However, it did not deny that there are major challenges in manufacturing CAR T cell products as well as in managing adverse effects.

The FDA assured that they are “leveraging the existing regulatory framework” to expedite the development of safe CAR T cell products. “There are multiple expedited programs available to the industry to help make safe and effective CART cells therapies available to cancer patients sooner” it said.

Recipient of the Image MMORE Award and Business First Forty Under 40 Award in Ohio, Dr. Hofmeister is very optimistic about this research and hopes to start clinical trials sometime this year. We hope to follow up with Dr. Hofmeister soon to learn further on the latest developments in his research on CAR T Cells.

 

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