A Solid Move for CAR T
CAR (chimeric antigen receptor) T-cell therapy has become an established treatment option for patients with hematologic cancers, demonstrating strong and lasting survival benefits in patients with limited options. Interestingly, researchers have struggled to elicit the same success in patients with solid tumours.
New data published in Nature leveraged a genome-wide CRISPR knockout screen to identify resistance pathways in solid tumours. By applying selective pressure with a CAR, researchers could determine which genes allowed tumour cells to evade CAR T-cell therapy.
This study revealed loss of interferon gamma pathway genes led to CAR T-cell therapy resistance, with results also replicated in knockout mice models. However, they noted the interferon gamma pathway did not impact the sensitivity of leukemia, lymphoma or multiple myeloma cancers.
Knowing solid and hematologic tumours respond differently to CAR T-cell therapy has the opportunity to inform future treatment decisions (e.g. targeting the interferon gamma pathway to improve responses in solid tumours, blocking the pathway to reduce CAR T-cell-related toxicities in hematologic cancers) – bringing this transformative therapy one step closer to even more patients!