title: Strengthened tumor antigen immune recognition by inclusion of a recombinant Eimeria antigen in therapeutic cancer vaccination.
abstract: The need for novel, effective adjuvants that are capable of eliciting stronger cellular and humoral adaptive immune responses to antigenic targets is well understood in the vaccine development field. Unfortunately, many adjuvants investigated thus far are either too toxic for human application or too weak to induce a substantial response against difficult antigens, such as tumor-associated antigens (TAAs). In spite of this trend, clinical investigations of recombinant Eimeria antigen (rEA) have revealed this protein to be a non-toxic immunogenic agent with the ability to trigger a Th1-predominant response in both murine and human subjects. Our past studies have shown that the injection of a rEA-encoding adenovirus (rAd5-rEA) alongside an HIV antigen-encoding adenovirus greatly improves the adaptive immune response against this pathogen-derived transgene. In this report, we investigated whether rAd5-rEA could promote and/or alter cytotoxic memory responses toward carcinoembryonic antigen (CEA), a colorectal cancer-related TAA. We found that the addition of rAd5-rEA to an Ad-based CEA vaccine induced a dose-dependent increase in several anti-CEA T and B cell responses. Moreover, inclusion of rAd5-rEA increased the number of CEA-derived antigenic epitopes that elicited significant cell-mediated and IgG-mediated recognition. These enhanced anti-CEA immune responses also translated into superior CEA-targeted cell killing, as evaluated by an in vivo cytotoxic T lymphocyte assay. Overall, these results suggest that co-administration of rAd5-rEA with a tumor antigen vaccine can substantially boost and broaden the TAA-specific adaptive memory response, thereby validating the potential of rAd5-rEA to be a beneficial adjuvant during therapeutic cancer vaccination.
authors: Department of Microbiology and Molecular Genetics, Michigan State University, 567 Wilson Road, 4194 Biomedical and Physical Sciences Building, East Lansing, MI, 48824, USA.
authors: Dionisia
authors: D
authors: Quiroga
authors: Yasser A
authors: YA
authors: Aldhamen
authors: Daniel M
authors: DM
authors: Appledorn
authors: Sarah
authors: S
authors: Godbehere
authors: Andrea
authors: A
authors: Amalfitano
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000276:Adjuvants, Immunologic; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology* / Q000517:prevention & control; D004539:Eimeria / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000091402:Prohibitins; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; C000717331:PHB2 protein, human; D000091402:Prohibitins; D011994:Recombinant Proteins
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