GAIA-102 cells, an off-the-shelf and highly activated NK-like cell product, elicit endogenous immune cell responses in solid tumor model 

[Background] We have developed a novel method for generating highly activated NK-like cells (GAIA-102) from mixed peripheral blood mononuclear cells. Currently, three Phase I clinical trials are being conducted on patients with solid tumors. In preclinical studies, GAIA-102 has demonstrated two anti-tumor mechanisms in preclinical studies: significant mass reduction and the establishment of anti-tumor-acquired immunity. However, the underlying mechanism remains to be elucidated. This study aims to understand the interaction between GAIA-102 and the host immune response. [Methods]CT26-GFP cells were intraperitoneally injected into Balb/c mice, followed by intraperitoneal administration of GAIA-102 with IL-2. After one or three treatment cycles, spleens were harvested and manually dissociated and then analyzed by flow cytometry to evaluate antigen-presenting cells(APCs) , including conventional dendritic cells (cDC) and macrophages. Additionally, CD4+ and CD8+T cells were isolated for CT26-specific T cell response Enzyme-Linked Immunospot (ELISPOT) assay. [Results]The treatment with GAIA-102 resulted in a substantial increase in cDC counts and induced a shift in the M1 macrophage phenotype. ELISPOT assays demonstrated dose-dependent enhancements in CT26-specific T lymphocytes(CTLs) response in GAIA-102 treated mice. [Conclusion] GAIA-102 therapy can stimulate the recruitment of effector APCs and enhance the CTLs response, aligning with our preclinical findings.