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TCRR > CAR-T vs TCR-210 and caveats...

TCR2 IPO hits midpoint, setting stage for trials of CAR-T rivals

By hitting its fundraising target, TCR2 has positioned itself to move three candidates into and through early-phase development. TCR2 plans to start testing TC-210 in patients with mesothelin-positive solid tumors imminently and get therapies against CD19-positive B-cell hematological malignancies and MUC16-positive solid tumors into the clinic by early next year.

As TCR2 sees it, CAR-T therapies are held back by their use of just one subunit of the TCR2 signaling complex and independence from normal T cell signaling mechanisms, leading them to overproduce cytokines.

TCR2 makes its cell therapies by fusing a cancer antigen recognition domain to a subunit of the T cell receptor (TCR). A lentiviral vector then transfers genetic information for TCR2’s TCR Fusion Construct into a patient’s own T cells. This results in T cells that zero in an a specific antigen. When the T cells find the antigen, TCR2 thinks they will harness the entire TCR, triggering a strong yet safe attack.

That idea has held up in preclinical tests but could come unstuck in a number of ways in the clinic. One theoretical concern is that the production process will expand a T cell that recognizes a patient’s own cells as invaders. Such a cell therapy could attack healthy tissues, potentially killing the patient.

TCR2 plans to exclude people with a history of severe autoimmune disease from its trials to mitigate the risk, but even then there is a slim chance it will produce autoreactive T cell therapies.