Vector-based delivery of tumor-associated antigens and T-cell co-stimulatory molecules in the induction of immune responses and anti-tumor immunity.
It has now been demonstrated in both experimental models and recent clinical trials that certain "self" antigens, which are functionally non-immunogenic in the host, can become immunogenic if presented to the immune system in a certain way. Here, we describe recombinant vaccines and vaccine strategies that have been developed to induce and potentiate T-cell responses of the host to such self-antigens. These strategies include: (a) the use of recombinant poxvirus vectors in which the tumor-associated antigen (TAA) is inserted as a transgene. Recombinant vaccinia vaccines and recombinant avipox (replication-defective) vaccines have been employed to break tolerance to a self-antigen; (b) the use of diversified prime and boost strategies using different vaccines; and (c) the insertion of multiple T-cell co-stimulatory molecules into recombinant poxvirus vectors, along with the TAA gene, to enhance T-cell immune responses to the TAA and induce anti-tumor immunity.
Hodge
James W
JW
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Grosenbach
Douglas W
DW
Schlom
Jeffrey
J
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005822:Genetic Vectors; D006801:Humans; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000951:Antigens, Neoplasm