OH… T CELL!

The following letter is in response to an Economist Article published on 2/20/2016.

Dear The Economist,

The elusive nature of cancer is notorious for its ability to evade the immune system. In your recent article, “Mr. T cell,” you mentioned the novel technology regarding CAR T cells in treating B cell cancers, because of their ability to recognize the CD19 marker on the transformed cells. The collateral damage would be a patient losing their normal B cells. Fortunately, this marker is only unique to B cells and they are expendable. The technology is moving fast; however, there is still much to be learned about T cell biology before it can be effectively translated in the clinic. I believe it is important to discern the properties of how our immune system mounts an attack on foreign entities. When our normal cells are infected with a virus, it starts to express foreign protein fragments on the surface, allowing our T cells to identify and kill through major histocompatibility class (MHC) restricted T-cell recognition. However, tumor cells are able to masquerade as normal cells and avoid this calamitous faith.  The engineered T cell, known as CAR T cells, are able to circumvent this ordeal by targeting surface molecules independently of MHC molecules, such as CD19, and induce an immune response once the CAR structure is engaged.

There is no perfect marker for cancer, resulting in toxicity through immune-mediated destruction. But, if the patient manages to survive this brute force method of immunotherapy, one important issue still arises with regards to the persistence of the CAR T cells in the patient. Since cancer is analogous to a chronic infection, CAR T-cells must be able to survive and persist to protect from recurrence. One of the extrinsic factors limiting CAR potency is T-cell exhaustion. We can attribute this ‘exhausted’ state due perpetual signaling in the CAR T cell from engagement on malignant cancer cells, which would lead to a negative effect on the development of memory T cell properties known to provide protective immunity for decades. Mr. T cell’s ability to be effective is also its Achilles’ heel.

 

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