CLTX-CAR T is a game changer, page-25

2020 CAR T landscape GBM

A good read to get an understanding of the types of CAR T's being evaluated by other researchers, effectively targeting IL13-Rα2, HER2, and EGFRvIII. This publication was written prior to CLTX being introduced into the clinic, as such it is not mentioned. But it does paint a good picture of how devastating GBM is and how little success humans have had against this very aggressive solid cancer.

I'd recommend reading the pre-clinical data published by Chimeric Therapeutics which discusses the shortcomings of the current approach, but in general can be summarised with antigen-escape being GBM's main defense that has so far held up against all man-kind has thrown at it.

But alluding again to the ability of CLTX to bind to GBM expressing a wide range of IL13-Rα2, HER2, and EGFRvIII... demonstrating that it possesses properties that surpass existing therapies targeting only these three antigens.

What I found interesting is that mice treated with CLTX CAR T who relapsed exhibited similar abilities to bind to CLTX CAR T as those who were untreated. That suggests that antigen escape as not the result of the relapse, rather a new cancer had formed.. which was not resistent to CLTX CAR T.

In my mind, GBM is like a weed. Current treatment may have some success in destroying the stem and leaves.. but the roots remain and the weed will grow again, with resistance to whatever weed killer you used the first time. The hope here is that CLTX CAR T is able to target the root of the weed.. and the pre-clinical work does suggest this potential.

But I feel we are at such an early stage of CAR T therapy, CLTX CAR T may only be the starting point in which combination therapy, such as combining CLTX CAR T with checkpoint inhibitors such as Tecentriq which blocks PD-L1. But first, they must establish that CLTX CAR T is safe and effective against GBM.