Feeder-Free TIL Therapy Cuts IL-2 Dependence, Boosts Safety

Researchers from the Senior Department of Oncology of Chinese PLA General Hospital and Shanghai Juncell Therapeutics have developed a groundbreaking feeder-free TIL expansion protocol that significantly reduces dependence on high-dose interleukin-2 (IL-2), a major hurdle in adoptive cell therapy for solid tumors. Published in Cancer Biology & Medicine, the study demonstrates that this approach generates functional tumor-infiltrating lymphocytes (TILs) across multiple solid tumor types, including melanoma, pancreatic, gastric, cervical, and colorectal cancers, while minimizing T-cell exhaustion. The protocol eliminates feeder cells and uses low-concentration IL-2 supplemented with IL-7 and IL-15, achieving expansion success rates of at least 90% and producing TILs with high purity and potent cytotoxic activity.

The team further showed that combining this feeder-free TIL therapy with low-dose PD-1 blockade significantly enhances anti-tumor activity in a colorectal cancer patient-derived xenograft model, with reduced tumor volume and improved tolerability compared to TIL therapy alone. This combination approach could replace the need for post-infusion high-dose IL-2, which is associated with severe toxicity. The study also explored hydroxychloroquine (HCQ) as an immunomodulatory agent, which upregulated MHC-I expression on tumor cells in vitro and enhanced early-phase TCR-T cell killing, though its in vivo benefit was limited.

These findings carry significant implications for making TIL therapy safer and more accessible. By simplifying manufacturing and reducing costs, the feeder-free, IL-2-sparing strategy could broaden the reach of TIL-based immunotherapies to a wider range of solid tumor patients. The lead authors emphasized that this approach addresses a critical unmet need, and if validated in clinical studies, could transform the landscape of adoptive cell therapy.