May 29 Preclinical Quick Takes: Vor debuts lead stem cell program; plus an inverse Alzheimer's-cancer target, and statins for cognitive defects

Vor Biopharma unveils lead candidate comprising CD33-deficient stem cells
Vor Biopharma Inc. co-founder Siddhartha Mukherjee at Columbia University showed transplantation of hematopoietic stem cells with genetic ablation of CD33 allowed CAR T or antibody therapy to kill acute myelogenous leukemia cells in mice without targeting the CD33-deficient HSCs. The approach, described in a Proceedings of the National Academy of Sciences paper, could repopulate healthy blood cells to reduce on-target immunotherapy toxicity and enable its broader use for hematologic malignancies. The HSCs are licensed to Vor and form the basis of its lead candidate, VOR33. Vor, a PureTech Health plc (LSE:PRTC) subsidiary, plans to combine CAR T therapies with HSCs modified to go unrecognized by CAR Ts (see "Beyond B Cells").

Deleting gene linked to Alzheimer's kills HER2+ cancer
University of Turku researchers reported in a Nature Communications paper that deleting SORL1 in HER2-positive cancer cells increases accumulation of HER2 in lysosomes, decreases oncogenic signaling and tumor growth, and increases sensitivity to cationic amphiphilic drugs. SORL1 mutations have been linked to β amyloid accumulation and Alzheimer's disease pathogenesis, suggesting an inverse relationship for the target between Alzheimer's and cancer...