Dacek MM, Kurtz K, Wallisch P, et al. Potentiating Antibody-Dependent Killing of Cancers with CAR T Cells Secreting CD47-SIRPα Checkpoint Blocker. Blood. 2023; (doi: 10.1182/blood.2022016101).
Chimeric antigen receptor (CAR) T-cell therapy, local CD47 inhibition, and orthogonally targeted monoclonal antibody each have limitations as a singular treatment, but they appear to have great potential when used together hematopoietic malignancies. Scientists engineered "Orexi" CAR T cells to release CV1, a high affinity blocker of CD47, at the tumor location. Local CV1 secretion, in turn, improved anti-tumor activity and potentiated an even greater effect derived from the addition of traditional CAR T cells plus antibody in xenograft models. CV1 released by the Orexi CAR T cells reversed immunosuppression of myelomonocytoid cells in vitro and in the tumor microenvrionment. The investigators believe local secretion of the CD47 blocker also may head off systemic toxicities.