Targeting of CCR8 induces antitumor activity as a monotherapy that is further enhanced in combination with a Listeria-based immunotherapy
Daniel O Villarreal1, Susan Armington1, Andrew L'Huillier1, Cristina Mottershead1, Kimberly Ramos1, Elena V Filippova1, Dipti M Kelkar1, Brandon D Coder1, Robert G. Petit1, Michael F Princiotta1
1Advaxis Immunotherapies, Princeton, NJ, 08540, USA
CCR8 is a chemokine receptor that is expressed principally on Treg cells and known to be critical for Treg function, as CCR8 regulatory T cells can drive immunosuppression. Recently, studies have demonstrated that CCR8 is uniquely upregulated in human tumor-resident Treg cells of breast, colon, and lung cancer patients compared to normal tissue-resident Treg cells. Therefore, CCR8 tumor-resident Treg cells are rational targets for cancer immunotherapy. Here, we demonstrate that monoclonal antibody therapy targeting CCR8 significantly suppressed tumor growth and improved long-term survival in two different tumor-bearing mouse models. The antitumor activity could be correlated with an increase of tumor-specific T cells, enhanced infiltration of CD4 and CD8 T cells, and a significant decrease in the frequency of intratumoral Tregs. Initial studies explored a combinatorial regimen using anti-CCR8 mAb therapy and a Listeria-based cancer vaccine. Anti-CCR8 mAb therapy synergized with the vaccine to significantly delay tumor growth and induced complete regression in 20% of the mice. These results suggest that CCR8 represents a promising target for cancer immunotherapy, either as a single agent or in combination with other forms of immunotherapy.