Colorectal cancers are the third leading cause of cancer-associated deaths in
the United States. Carcinoembryonic antigen (CEA) is a glycoprotein which is overexpressed
in all adenocarcinomas of the colon and rectum and is extensively used as a
serologic marker of colon cancer. Its presence in the normal fetal colon, as well as in
gut crypts and healing intestinal mucosa of adults makes it a challenging immunologic
target, as cytotoxic T lymphocytes (CTL) must overcome tolerance and be directed
towards CEA-expressing cancer cells while sparing normal CEA-expressing cells.
CAP1-6D, a unique 9-mer peptide of the CEA protein with a single amino acid
mutation has been identified as a tumor specific antigen that can induce a stronger
immune response than the wild type CEA peptide. Costimulatory signals, such as B7.1
are also critically important in the generation of an effective T cell response to any
antigen. The cytokine GM-CSF is a useful vaccine adjuvant for its ability to increase
antigen-presenting cells and enhance the antigen-specific anti-tumor response.
Additionally, interferon-alpha as an adjuvant can enhance the expression of tumor
antigens, such as CEA. This chapter describes the rationale for a clinical trial in which
two virus-based CEA vaccines encoding the CAP1-6D peptide as well as costimulatory
molecules (B7.1, ICAM-1, and LFA-3) were administered along with the vaccine
adjuvants interferon-alpha and GM-CSF.
Keywords: Carcinoembryonic antigen, Clinical trial, Colorectal cancer,
ELISPOT assay, Interferon-alfa, Recombinant vaccines, Tumor immunotherapy,
Viral vector.
