Cytokine adjuvanation of therapeutic anti-tumor immunity targeted to cancer mucosa antigens.
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.
Snook
Adam E
AE
Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Huang
Lan
L
Schulz
Stephanie
S
Eisenlohr
Laurence C
LC
Waldman
Scott A
SA
D000818:Animals; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000276:immunology*; D007114:Immunization; D007376:Interleukin-2 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide / Q000276:immunology*
D007376:Interleukin-2; D018000:Receptors, Peptide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled