Metastatic cancer remains the main cause of cancer-related mortality. Therapies are needed to address this significant unmet medical need. The implantation of cancer cells resulting in metastatic foci is the consequence of a multistep process that is seldom diagnosed or targeted for therapeutic intervention. In light of its adhesive properties and deregulated overexpression by cancer cells, the carcinoembryonic antigen (CEA) has been identified as a molecular determinant linked to cellular events defining the metastatic cascade including their attachment to the ECM and to the formation of micrometastases. Herein, we report that a vaccination strategy yielding an antigen-specific TH9 response induces long term host surveillance and prevents the engraftment of circulating cancer cells. Specifically, we show that vaccination with a recombinant CEA IgV-like N domain, formulated with the TLR3 ligand poly I:C, elicits a CEA-specific TH9 response, wherein IL-9 secreting TH cells act in concert with CEA N domain-specific antibodies as well as activated mast cells in preventing tumor cell engraftment. Vaccine-imparted protection was reversed upon depleting CD3+ T cells, neutralizing serum IL-9, pharmacologically stabilizing or by depleting of CD117+ mast cells, in vivo. The development of this immune response was dependent on TLR3, since interference with the TLR3-dsRNA complex formation led to a reduction in vaccine-imparted protection and a shift in the resulting immune response toward a TH2 response. These results highlight the first instance of a vaccine induced tumor antigen-specific TH9 immune response and points to the existence of an alternate tumor eradication mechanism that may be exploited for developing anti-metastasic immunotherapies. (Supported by OCIR-IPDC,CBCF and CIHR)
Citation Format: Aws Abdul-Wahid, Aaron Prodeus, Marzena Cydzik, Mays Alwash, Jean Gariepy. A vaccine-induced, antigen-specific TH9 immune response blocks tumor cell engraftment [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A029.
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