Biotech Values

[DewDiligence]

(GILD/NVS/etc)—NEJM editorial on the state of CAR-T:

http://www.nejm.org/doi/full/10.1056/NEJMe1714680

The final paragraph speaks to the shortcomings of existing CAR-T designs in solid tumors and the promise of targeting neoantigens to overcome these limitations:

CAR-engineered T cells are a revolutionary treatment for patients with advanced blood cancers. Unfortunately, CAR-engineered T cells have been largely ineffective in patients with metastatic solid cancers, which account for the majority of cancer-related deaths. One major factor contributing to this lack of efficacy is the paucity of suitable cell-surface molecules that are expressed by solid cancers for CARs to target.

This roadblock can be overcome by engineering T cells with T-cell receptors that can recognize tumor-specific antigens derived from intracellular proteins, such as neoantigens arising as a consequence of somatic mutations expressed by tumors, which are found in the majority of patients with metastatic epithelial cancers. T cells that are genetically modified to express T-cell receptors targeting mutated neoantigens may represent a new wave of promising and highly personalized gene-engineered T-cell therapies for patients with metastatic solid cancers.