Clinical efficacy of adoptive immunotherapy by IL-4 activated tumor-infiltrating lymphocytes in patients with advanced cancer

Background Adoptive immunotherapy using tumor-infiltrating lymphocytes (TILs) has been used to treat malignant melanoma and renal cell carcinoma, although the clinical efficacy of this method has not yet been proved. To improve clinical efficacy, it is important to induce sufficient amounts of tumor-infiltrating lymphocytes to fight the tumor. In this study, we investigated the clinical efficacy of adoptive immunotherapy using interleukin (IL)-2 activated tumor-infiltrating lymphocytes combined with IL-4. Methods Tumor-infiltrating lymphocytes from patients with non-malignant melanoma and non-renal cell carcinoma were cultured with IL-2 monotherapy (n=10) and combination therapy with IL-4+IL-2 (n=20). Comparing the 2 groups, we investigated the clinical benefits of adoptive immunotherapy, considering safety, clinical efficacy, survival periods, and quality of life. Results By using the IL-4+IL-2 combination, we successfully transferred 6.5 times more activated tumor-infiltrating lymphocytes, as compared to cell counts using IL-2 monotherapy. The response rate achieved was 58.8% (2 complete and 8 partial responses) without any side effects in the IL-4+IL-2 group. Furthermore, the IL-4+IL-2 group had longer survival periods and improved quality of life, compared to the IL-2 monotherapy group. Conclusion The IL-4+IL-2 combination improved the clinical efficacy of adoptive immunotherapy, and improved quality of life in patients with non-malignant melanoma and non-renal cell carcinoma.