CAR T Cells Calibration May Boost Therapy Potency

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Immunotherapies that use Chimeric Antigen Receptor (CAR) T cells could soon become even more effective as scientists have found that changing the number of amino acid sequences can give them increased customization options.

These genetically engineered human immune cells have been very forceful in dealing with several forms of cancer, especially leukemia and lymphoma. Similar to our own natural antibodies, CAR was designed with parts from T cell receptors. Depending on specific needs, one of two proteins is spliced to the basic chassis, either CD28 or 41BB. It seems CARs with CD28 tend to be quicker killers, while those coded with 41BB are more sluggish but also more enduring.

Now, researchers from Memorial Sloan Kettering led by immunologist Michel Sadelain reported they could modify the current CAR model to improve its performance. By controlling the number of amino acid sequences called ITAMs from within CD28-based CARs, these can become more persistent.

Current CAR designs come with three ITAMs”, explained Dr. Sadelain. “We found that by varying the number of working ITAMs, we could increase the longevity of the CAR T cells without compromising their tumor-killing power”.

The goal is to enhance the therapeutic profile of CAR treatments which would lead to increased response rates, especially for people battling leukemia, but also make them more viable against other cancers.

Early tests conducted on mouse models showed the number of ITAMs present in a CAR played a big part in shaping which path the cell took – either rapidly engaging the tumors, or creating a slower but more organized response.

At the moment, immunotherapies appear to have the biggest potential when it comes to addressing oncological problems. As they employ the body’s natural defense system, they are safer and have fewer side effects compared to standard options (radiation and chemotherapy). Having the ability to customize their structure means doctors could soon have a wider variety of weapons in the fight against malignancies.