![]() Identification of novel subdominant epitopes on the carcinoembryonic antigen recognized by CD4+ T cells of lung cancer patients. Phase I clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer. Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM poxviral-based vaccines in patients with metastatic carcinoma. Balancing between antitumor efficacy and autoimmune pathology in T-cell-mediated targeting of carcinoembryonic antigen. Enhancement of cytotoxic T-lymphocyte responses in patients with gastrointestinal malignancies following vaccination with CEA peptide-pulsed dendritic cells. Breast cancer vaccines: a clinical reality or fairy tale? Ann Oncol 2006 17: 750– 62. ![]() Vaccines for cancer prevention: a practical and feasible approach to the cancer epidemic. ![]() The carcinoembryonic antigen IgV-like N domain plays a critical role in the implantation of metastatic tumor cells. A focused immune response targeting the homotypic binding domain of the carcinoembryonic antigen blocks the establishment of tumor foci in vivo. Carcinoembryonic antigen as a target for therapeutic anticancer vaccines: a review. Hallmarks of cancer: the next generation. Parallel progression of primary tumours and metastases. The metastatic niche: adapting the foreign soil. These findings point to the existence of an alternate tumor targeting immune mechanism that can be exploited for the purpose of developing vaccine therapies targeting tumor dissemination and engraftment. 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 T H2 response. 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 T H9 response, wherein IL-9 secreting T H cells act in concert with CEA N domain-specific antibodies as well as activated mast cells in preventing tumor cell engraftment. In this study, we establish that a vaccination strategy yielding an antigen-specific T H9 response induces long term host surveillance and prevents the engraftment of circulating cancer cells. The engraftment of circulating cancer cells at distal sites represents a key step in the metastatic cascade, yet remains an unexplored target for therapeutic intervention.
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