Anti-TNFR2 antibody and HMGN1 combined with TIL cell therapy inhibits colorectal cancer progression by enhancing immune response.

BACKGROUND

Immunotherapy utilizing tumor-infiltrating lymphocytes (TILs) has demonstrated exceptional effectiveness in the treatment of diverse solid tumors. However, existing procedures typically involve lymphodepleting chemotherapy using cyclophosphamide and high-dose IL-2 to support the proliferation and activity of reintroduced TILs, despite the common occurrence of systemic toxicity.

METHODS

A CT26 colorectal cancer mouse model was established in this research. Tumor tissues were removed, and TILs were isolated and cultured in vitro. The TIL identity was validated via flow cytometry. Mice received treatment with an anti-TNFR2 antibody, HMGN1, and TILs to assess the effectiveness of this new immune-combination therapy against tumors. Flow cytometry was employed to analyze CD8 T cells, CD4 T cells, and Treg cells, with TIL function evaluated using CCK8 assays.

RESULTS

Administration of anti-TNFR2 antibody and HMGN1 not only stimulated TIL proliferation but also suppressed Treg cells within tumor tissues, thereby markedly enhancing TIL-mediated anti-tumor activity in mice. Mice receiving this combination therapy achieved complete tumor eradication and significantly prolonged survival. This immune-combination therapy also demonstrated substantial tumor suppression in the 4T1 breast cancer mouse model.

CONCLUSION

The combined treatment of the anti-TNFR2 antibody and HMGN1 therapy synergistically alleviates immunosuppression by decreasing tumor-infiltrating regulatory T cells (Treg cells). This decrease in Treg cells results in the successful eradication of tumors in vivo by promoting the function and expansion of TIL.