Open AccessCytokine Adjuvanation of Therapeutic Anti‐tumor Immunity Targeted to Cancer Mucosa Antigens
Author(s) -
Snook Adam E.,
Huang Lan,
Schulz Stephanie,
Eisenlohr Laurence C.,
Waldman Scott A.
Publication year - 2008
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/j.1752-8062.2008.00054.x
Subject(s) - medicine , immunology , immune system , cancer , antigen , cancer vaccine , immunotherapy , immunogenicity , immunization , cancer immunotherapy , colorectal cancer , cancer research , viral vector , biology , recombinant dna , biochemistry , gene
Colorectal cancer immunotherapy is limited by the paucity of available target antigens fulfilling the necessary criteria of tumor‐specificity, sufficient immunogenicity and universal association with disease. A novel class of immune targets, cancer mucosa antigens (CMAs), whose expression normally is confined to mucosae but maintained during neoplastic transformation, promises to overcome these imitations, enjoying the advantage of immune compartmentalization, preventing autoimmune disease, while permitting therapeutic anti‐tumor responses. Indeed, therapeutic immunization against the model CMA guanylyl cyclase c (GCC) extends survival in mouse models of established parenchymal colorectal cancer metastases with antitumor efficacy superior to currently available antigens. Here adjuvanation of therapeutic antitumor immunity to GCC was explored employing the cytokines IL‐2 and GM‐CSF in a mouse model of metastatic colorectal cancer. Combining plasmids expressing murine IL‐2 or GM‐CSF with recombinant viral vector immunization to GCC enhanced antitumor efficacy beyond viral vector immunization alone. These studies support the incorporation of IL‐2 and GM‐CSF in CMA‐targeted immunization regimens for established colorectal cancer metastases.