Targeting tumor vasculature: expanding the potential of DNA cancer vaccines.
Targeting the tumor vasculature with anti-angiogenesis modalities is a bona fide validated approach that has complemented cancer treatment paradigms. Tumor vasculature antigens (TVA) can be immunologically targeted and offers multiple theoretical advantages that may enhance existing strategies against cancer. We focused on tumor endothelial marker 1 (TEM1/CD248) as a model TVA since it is broadly expressed on many different cancers. Our DNA-based vaccine approach demonstrated that CD248 can be effectively targeted immunologically; anti-tumor responses were generated in several mouse models; and CD8(+)/CD4(+) T cell responses were elicited against peptides derived from CD248 protein. Our work supports our contention that CD248 is a novel immunotherapeutic target for cancer treatment and highlights the efficient, safe and translatable use of DNA-based immunotherapy. We next briefly highlight ongoing investigations targeting CD248 with antibodies as a diagnostic imaging agent and as a therapeutic antibody in an early clinical trial. The optimal approach for generating effective DNA-based cancer vaccines for several tumor types may be a combinatorial approach that enhances immunogenicity such as combination with chemotherapy. Additional combination approaches are discussed and include those that alleviate the immunosuppressive tumor microenvironment induced by myeloid-derived suppressor cells and T regulatory cells. Targeting the tumor vasculature by CD248-based immunological modalities expands the armamentarium against cancer.
Ovarian Cancer Research Center (OCRC), University of Pennsylvania School of Medicine, Biomedical Research Building II/III, 13th Floor, 421 Curie Blvd., Philadelphia, PA, 19104, USA.
Stefano
S
Ugel
John G
JG
Facciponte
Francesco
F
De Sanctis
Andrea
A
Facciabene
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000627:therapeutic use
D015703:Antigens, CD; D000951:Antigens, Neoplasm; C078203:CD248 protein, human; D019496:Cancer Vaccines; D019444:Vaccines, DNA