Consider endogenous TCR KO

[hammer]

When I discussed this work at a high level with Alex Marson he was quite skeptical that we should see T cell killing for 4 different TCRs without having to KO the endogenous TCR for any of them. He claims that his lab has found the requirement for endogenous TCR KO to be TCR-dependent but quite common. If we are going to expend the energy to KO HLA from the cancer cell line, we may as well try to KO the endogenous TCR from the T cells.

[pinarden]

It's interesting to hear that the KO requirement is TCR-dependent. In any case, we have good preliminary data with the OT-I TCR both for mouse T cells and human T cells. Because we are not interested in achieving the highest cytotoxicity but we're interested in showing that these TCRs are reactive to those peptides, we can bypass endogenous TCR KO. If our first trial fails, then we should consider this. Thank you!