Replies to post #154 on TScan Therapeutics Inc (TCRX)

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No, but there could be merit in using the (TCR) approach in a select population of patients who unable to undergo an HSCT.

In AML that would be patients at a high risk of relapse, as defined by CR following induction, but are MRD+, and/or with incomplete recovery of neutrophil (CRi) or platelet counts (CRp). In that group more than 80% will relapse within the first year no matter what is (currently) done after induction therapy https://ascopubs.org/doi/full/10.1200/JCO.2014.58.3518

I also know of a PhI/II trial testing auto CD8+ (central memory vs. naïve phenotype) T-cells transduced using a viral vector to target WT1. Of seven treated, four are NED, with the other three relapsing. There are data from two (the third declined additional treatment before passing away) showing one was due to WT1 negative disease and the other was due to failure of T-cells.

WT1 is an oncogene and also expressed on leukemic stem cells https://www.nature.com/articles/nature22993

Looking at the patient who was WT1 negative, their disease was found to express CCNA1, so could be targeted with a different TCR https://ashpublications.org/bloodadvances/article/4/2/387/440610/Evaluation-of-cyclin-A1-specific-T-cells-as-a

As for the second, immunosuppressive and rapid proliferation of the disease were likely the reason, so other modifications to T-cells will be needed to address both, such as this https://ashpublications.org/blood/article/130/22/2410/36564/A-CD200R-CD28-fusion-protein-appropriates-an