Overview
- MIT and Harvard researchers report in Nature Communications a one-step design that combines siRNA HLA class I knockdown with a CAR plus PD-L1 or single-chain HLA-E on a single DNA construct.
- In humanized-mouse lymphoma models, the engineered donor CAR-NK cells persisted for at least three weeks and nearly eliminated tumors, outperforming unmodified or CAR-only NK cells rejected within two weeks.
- The modified cells showed lower propensity for cytokine release syndrome compared with conventional approaches in the preclinical tests.
- The approach is intended to enable off-the-shelf CAR-NK products by reducing host rejection and simplifying manufacturing steps relative to patient-derived cell therapies.
- The team, led by senior authors Jianzhu Chen and Rizwan Romee with lead author Fuguo Liu, is preparing clinical trials with Dana-Farber and collaborating with a biotech to explore applications such as lupus.