CAR-T cell therapy as it stands today requires preceding lymphodepletion, often in the form of chemotherapy, to reduce competition from innate T cells thereby creating for the engineered T cells an environment ripe for the taking. It goes without saying that the lymphodepletion part in and of itself carries considerable risk. Enter therapeutic T cells engineered with IL-2 and IL-9, put to the test in murine models of melanoma and pancreatic cancer. What’s special about these particular brands of interleukins? They take on a unique mix of both stem-cell qualities, allowing them to outcompete existing chemo-naive lymphocyte populations, as well as the killer-like qualities we all know and love so they can simultaneously carry out their primary duty of destroying cancer cells. Here the IL-9 additive showed particularly impressive tumor-killing efficacy, laying the groundwork for a whole new paradigm of CAR-T cell therapy for solid tumors sans conditioning chemotherapy.
- Kalbasi, Nature 2022