HLA-independent TCRs with increased antigen sensitivity; plus Synthekine, Luminary and more

A Memorial Sloan Kettering Cancer Center team, including Mnemo Therapeutics co-founders Michel Sadelain and Isabelle Rivière, designed HLA-independent TCRs to target tumor cells with low antigen density. The researchers edited the TRAC locus in human peripheral blood T cells to insert a new antigen receptor construct whose extracellular domain links immunoglobulin heavy and light chains to TCR constant regions. In xenograft mouse models of leukemia, the HLA-independent T cell (HIT) receptors outperformed matched CD28-based CARs in recognition and killing of tumor cells with low density cell surface antigen expression. The findings are published in Nature Medicine.

Two teams published in Science Translational Medicine CD19-specific CAR T cells expressing a mutated IL2RB that can only be activated by a modified, orthogonal IL-2.  Synthekine Inc. showed its orthogonal human IL-2, STK-009, drove activation, expansion and antitumor efficacy of CAR T cells in a mouse model of lymphoma.  University of Pennsylvania and Stanford University scientists reported their orthogonal human IL-2 rescued the antileukemic effect of an otherwise suboptimal dose of CAR T cells.
Both approaches limited systemic toxicity...