Abstract A006: Understanding the Potential of Human IL-12 and Chimeric IL-15 Combination for Cancer Immunotherapy

• Published in: Cancer immunology research 2023-12, Vol.11 (12_Supplement), p.A006-A006
• Main Authors: Sharma, Priya Chandramohan, Patel, Digna, Dalai, Sarat K
• Format: Article
• Language: English
• ISSN: 2326-6074; 2326-6074
• DOI: 10.1158/2326-6074.TUMIMM23-A006

Autologous cell-based therapy is a preferred approach for Cancer immunotherapy. However, generating potent NK cells and antigen experienced T cells has been a challenge. To address this issue, we have developed a strategy of using the combination of IL-12 and IL-15 to activate CD4+ T cells, CD8+ T cells and NK cells. IL-12 and IL-15 possess distinct roles but both are potent inflammatory cytokines. IL-12 is a vital promoter of Th1 differentiation via activation of signal transducer and activator of transcription 4 (STAT4), while IL-15 is essential for developing innate immune response as well as contributing to the maintenance of memory CD8+ T cells. Substantial in vivo and in vitro data have been reported to support the role of IL-15 as a T cell growth factor. These activities of IL-12 and IL-15 make them ideal for combinatorial immunotherapy of cancer. However, the short half-life (~ 1hr) and poor bioavailability limits the therapeutic use of IL-15. To overcome these limitations, we have designed chimeric IL-15-IgG2 (Indian Patent Application No. 201721010096A) with an objective of augmenting the generation of memory T cells as well as reactivating them during the antigenic challenge. Our stable chimeric IL-15 has a half-life of >40 Hrs. In humans, IL-12 is needed for DCs to provoke rapid IFN-g production by NK cells, IL-15 seems essential for the NK cell proliferation. In the present study, we are testing the potential of chimeric IL-15 individually and in combination with native hIL-12 as an activator of CD4+ T cells, CD8+ T cells and NK cells. The combination of both cytokines shows potent release of IFN-g as well as activation of the T-cell subsets and NK cells. In our future studies we will use these pre-activated cells for adoptive transfer in cancer immunotherapy. Detailed findings will be reported during the conference. Citation Format: Priya Chandramohan Sharma, Digna Patel, Sarat K Dalai. Understanding the Potential of Human IL-12 and Chimeric IL-15 Combination for Cancer Immunotherapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr A006.