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Thursday, October 19, 2023

convertible CARs

This my second post on CAR T-cells. The first discussed modifying them so that don't have checkpoints and are prepared for nitic oxide. The aim is to make a super CAR T-cell which functions in the solid tumor micro-environment.

This second post is a semi-crazy idea about making off the shelf CAR T-cells rather than modifying cells from the patient. The cost of the patient specific therapy is not prohibitive even now and should go down the learning curve. However, my proposal of multiple modifications would add to the cost and why do them again and again ?

So the idea is to make a CAR T-cell line which will not be rejected by the patient even though the CAR T-cells are made with someone else's T-cells with different surface antigents especially different HLA antigens. Long ago my late father thought of deleting the Beta 2 microglobulin gene so that HLA A B and C would not be expressed on the surface. Here I make a much more radical proposal (which will never be allowed so it is just for a blog post)

The off the shelf CAR can be designed to express the do not kill me signal PDL1. As I already proposed that the receptor PD1 be deleted, these cells will not tell each other not to kill. I think that these cells could be infused into anyone and would function. They would also be dangerous - if some became leukemic dealing with them would have to include anti PDL1. Recall that I propose inserting Herpes TK into the super CAR T-cells so that they can be killed, if necessary, with gangcyclovir. That would be even more clearly needed with the PDL1 expressing super CAR T-cells.

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