Abstract A48: Subcutaneous injection of aGalCer loaded mature dendritic cells at near regional lymph node area leads tumor regression in the patients with malignant tumor
Authors: Ito Yoshinori , Noguchi Katsuo 
Published: December 2022

Abstract
Natural Killer T (NKT) cells are unique lymphocyte lineage that present both NK and T cell phenotype. NKT cells hold strong anti-tumor ability. To elicit NKT cells responses in cancer patients, adoptive transfer of a-galactosyl ceramide loaded APCs (aGalCer APCs) was exploited in a decade. In previous reports, intravenous injection of aGalCer APCs and submucosal injection were mainly evaluated. However, subcutaneous (SC) route of aGalCer APCs injection was not evaluated yet. We assumed subcutaneous injection of aGalCer loaded mature dendritic cells (aGalCer DC) might be effective and evaluated safety, anti-tumor effects and immune responses induced by SC injection of aGalCer DC. Methods: Autologous mononuclear cells were isolated by leukapheresis and then separated by Ficoll-Hypaque centrifugation. Plastic adherent monocytes were cultured for 6 days for differentiation into DC. The cells were cultured for an additional day for maturation with aGalCer loading. After cultivation, all cells were frozen and stored in liquid nitrogen until use. For tumor treatment, patients were injected aGalCer DC at least 4 times via SC (0.6-4.1 x 107 cells per injection) with 2 weeks interval. We evaluated safety and efficacy of aGalCer DC immunotherapy by CTCAE, tumor maker, RECIST and immunological analysis. Thirty-seven patients were enrolled in this immunotherapy between 2020-2021. Thirteen cases were treated by immunotherapy with cytotoxic chemotherapy. Three cases were treated immunotherapy with radiotherapy. 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 63.6% of evaluated cases and also increased numbers of CD8 cells and/or NK cells were observed in 88.5% of evaluated cases. Number of CD3+CD56+ positive cells in peripheral blood called as circulating NKT-like cells (cNKT) was up-regulated in 80.1% of patients whom injected aGalCer DC SC. We obtained CR case in chemotherapy naïve DLBCL patient. The patient had systemic multiple lymph node (LN) swelling. We injected aGalCer DC SC at axillary and inguinal region. After 6 injections, multiple LN swelling was disappeared completely and sIL2R was normalized. In another case, triple negative breast cancer with axillary LN metastasis, we obtained rapid tumor regression with aGalCer DC SC at axillary region. However, this anti-tumor effect was abolished by additional oral 5-FU. In the case combined aGalCer DC SC with liposomal doxorubicin, any of cNKT, CD8, NK upregulation was not obtained. In the all cases combined aGalCer DC SC with taxane or gemcitabine regimen, cNKT and CD8/NK upregulation were observed. Conclusion: aGalCer DC SC at regional lymph node area led tumor regression in several cases. aGalCer DC SC efficiently induced immune responses and anti-tumor effects even small amounts of aGalCer DC injection. The combination aGalCer DC SC with taxane/gemcitabine-based regimen might be feasible and useful for aGalCer DC immunotherapy.
Citation Format: Yoshinori Ito, Katsuo Noguchi. Subcutaneous injection of aGalCer loaded mature dendritic cells at near regional lymph node area leads tumor regression in the patients with malignant tumor [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr A48.