Abstract 3197: Adoptive T cell therapy using IL-7 and IL-15 expanded HER2-specific CD4 T cells for metastatic breast cancer

Abstract BACKGROUND: Adoptive cell therapy (ACT) has had limited success due to low T cell infiltration in breast cancer (BC) patients. We have shown that administration of class II HER2 peptide pulsed type I polarized dendritic cell (DC1) vaccines leads to increase in CD4 T cells in the periphery of BC patients. In this study, we investigated the feasibility of expanding CD4 T cells from peripheral blood mononuclear cells (PBMC) of HER2-DC1 vaccinated BC patients. METHODS: PBMCs from BC patients receiving HER2-DC1 vaccines were used for CD4 T cell expansion. PBMCs were co-cultured with HER2-DC1 at 10:1 ratio for initial activation followed by expansion with cytokines- IL-2 and IL-7 or IL-15. Expanded T cells were assessed for immune marker phenotyping by flow cytometry and TCRvb analysis. For TCRvB analysis, pre, post DC1, IL-7 and IL-15 expanded CD4 T cells were pelleted for DNA isolation and sequenced using Immunoseq Analyzer platform. In addition, we investigated the in vivo efficacy of adoptively transferred mouse IL-7/IL-15 expanded Her2 specific CD4 T cells in HER2+ TUBO mouse model. RESULTS: Co-culturing of patient PBMCs with HER2-DC1 in the presence of cytokines IL-2, IL-7 and IL-15 expanded CD4 T cells ranging from 8-43 fold expansion in different samples with 92-98% CD4 phenotype. CD4 T cells expanded in IL-7 had stem like memory phenotype while IL-15 skewed to terminally differentiated CD4 T cells. IL-7 expanded T cells had significantly higher Tim3 and Ox40 expression, and effector memory proportion as compared to the IL-15 expanded T cells. Restimulation of expanded T cells with HER2 pulsed DCs showed HER2 specificity as measured by increased interferon-gamma production We identified top five clones in PBMCs from DC1-HER2 vaccinated BC patients compared to baseline. We observed differential abundance of TCR clones under IL-7 and IL-15 conditions and identified unique clones for IL-7 and IL-15. ACT using a combination of IL-7 and IL-15 expanded mouse CD4 T cells led to 50% tumor regression in HER2+ model. CONCLUSION: These studies demonstrate that HER2 specific CD4 T cells can be successfully expanded from HER2-DC1 vaccinated patients. Post HER2 DC1 vaccine can generate a pool of antigen specific CD4 T cells and may offer a promising ACT for HER2 BC. Further studies are warranted to demonstrate the efficacy in the clinical setting. Citation Format: Namrata Gautam, Krithika Kodumudi, Colin Snyder, Amber Beyer, Ricardo Costa, Heather Han, Brian Czerniecki. Adoptive T cell therapy using IL-7 and IL-15 expanded HER2-specific CD4 T cells for metastatic breast cancer [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 3197.