Abstract 3186: Anti-tumor effects and immunological responses by aGalCer loaded antigen presenting cell infusion in the patients with malignant tumor

Abstract

Abstract Natural Killer T (NKT) cells are unique lymphocyte lineage that present both NK and T cell phenotype. NKT cells hold strong direct cytotoxic ability toward tumor cells through glycolipid/CD1d complex on tumor cells, NKT cells secrete large amounts of IFNγ and stimulate CD8 and NK cells as indirect cytotoxic effects. To elicit NKT cells responses in cancer patients, adoptive transfer of α-galactosyl ceramide (αGalCer) loaded APCs was exploited in a decade. I summarized anti-tumor effects and immune reaction treated with this therapy in recent 3 years. Methods: For αGalCer loaded APCs, CD14-monocyte (MO) or mature dendritic cells (DC) was used. Monocytes isolated by leukapheresis were purified ether plastic adherence or CD14-positive selection. Plastic adherent monocytes were cultured for 6 days for differentiation into DC, then for an additional day for maturation with αGalCer loading. CD14-Mo was cultured for 2 days with GM-CSF and αGalCer. After cultivation, all cells were frozen and stored in liquid nitrogen until use. For tumor treatment, patients were injected αGalCer-DC at least 4 times via SC with 2 weeks interval or injected at least twice with αGalCer-CD14-Mo intravenously with 3-4 weeks interval. We evaluated safety and efficacy of αGalCer-APCs immunotherapy by CTCAE, tumor maker, RECIST and immunological analysis. Fifty patients were enrolled in this immunotherapy between 2020-2022. Results: In all cases, we could not observe any therapy-related adverse effects above CTCAE Grade 2. Several anti-tumor effects such as tumor marker reduction and/or tumor regression including CR were observed in 60.6% of evaluated cases. In the cases with iv injection of αGalCer-CD14-Mo, CD3+CD56+ circulating NKT (cNKT) cells were significantly increased after the therapy. In the cases with subcutaneous injection of αGalCer-DC, NK number was significantly increased. Also, cNKT cells and CD8 cells were increased with tendency of significance after the therapy. We obtained CR case in chemotherapy naïve DLBCL patient by αGalCer-DC therapy. After 6 injections, multiple LN swelling was disappeared completely. In another cases, breast cancer with axillary LN metastasis, we obtained rapid tumor regression with αGalCer-DC SC injection. In the case combined αGalCer-APCs with some cytotoxic chemotherapy or conventional radiation immune responses were abolished. In the cases combined αGalCer-APCs with taxane, platinum, gemcitabine-based chemotherapy, immune responses were clearly observed. Conclusion: αGalCer-APCs infusion efficiently promote cNKT response. cNKT response was clearly related with immune responses such as CD8/NK upregulation and anti-tumor effects. Immune responses induced by the therapy seemed to be abolished by combined conventional radiotherapy or several cytotoxic chemotherapies. αGalCer-APCs infusion might be promising for cancer therapy. Citation Format: Yoshinori Ito. Anti-tumor effects and immunological responses by aGalCer loaded antigen presenting cell infusion in the patients with malignant tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3186.