Background CCL22 is a macrophage-derived chemokine that exerts immunosuppressive functions by the recruitment of regulatory T cells (Treg) through the CCL22/CCR4 axis. It has been described to play a key role in the suppression of anti-cancer immunity in different cancer types including ovarian, breast, or pancreatic cancer and is thought to promote the suppression of anti-cancer immunity by Treg recruitment. Recently, we described that CCL22-specific T cells generated from cancer patients can kill CCL22-expressing tumor cells and directly influence the level of CCL22 in vitro.1 In this study, we provide PoC data for a CCL22-targeting vaccine by assessing the immunotherapeutic efficacy of this approach in syngeneic mouse tumor models.
Materials and Methods Peptide vaccines that induce expansion of CCL22-specific T cells were identified by measurement of vaccine-induced ex vivo response (IFNγ ELISpot) in BALB/c and C57BL/6 mice. The antitumor efficacy was evaluated in CT26, Pan02 and B16 syngeneic models. To investigate the vaccine’s mode of action, the tumor immune infiltration was analyzed through flow cytometry and qPCR.
Results Vaccination with CCL22-specific peptide vaccines induced expansion of primarily CD8+, CCL22-specific T cell responses (assessed by ex vivo IFNγ ELISpot). Treatment with CCL22 vaccines reduced tumor growth and increased survival in CT26, Pan02 and B16 tumor models. Assessment of gene expression in the tumors indicated that vaccination leads to a reduction of CCL22 expression in the tumor microenvironment (TME), as well as the expression of other immune-suppressive molecules such as IDO. Furthermore, vaccinated mice harbored an increased CD8+ T cell infiltration with a concomitant increase in M1/M2 ratio within the TME.
Conclusions This study provides evidence that targeting CCL22 expressing cells by vaccination induces immune modulation in the TME, leading to augmentation of anti-tumor responses - thus provides a rationale for a novel immunotherapeutic approach in cancer.
Disclosure Information I. Lecoq: A. Employment (full or part-time); Modest; IO Biotech. K.L. Kopp: A. Employment (full or part-time); Modest; IO Biotech. R. Christensen: A. Employment (full or part-time); Modest; IO Biotech. E. Martinenaite: A. Employment (full or part-time); Modest; IO Biotech. A.W. Pedersen: A. Employment (full or part-time); Modest; IO Biotech. M.H. Andersen: A. Employment (full or part-time); Modest; IO Biotech.
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