ORLANDOA promising approach in vector vaccine development is the use of a combination of vaccination strategies that enhance T-cell responses for specific tumor-associated antigens, said Jeffrey Schlom, PhD, chief of the Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institutes, Bethesda, Maryland.
Dr. Schlom spoke at a symposium on cancer vaccines held in conjunction with the 38th Annual Meeting of the American Society of Clinical Oncology (ASCO) and sponsored by Antigenics Inc. and the University of Connecticut School of Medicine.
"Because tumor-associated antigens are, by definition, either weakly immunogenic or functionally nonimmuno-genic, vaccine strategies must be developed in which the presentation of the antigens to the immune system results in far greater activation of T cells than is being achieved naturally in the host," Dr. Schlom said.
He described a number of vaccine strategies that have been used to enhance T-cell responses to specific antigens. Vectors have been used to provide more efficient delivery of tumor-associated antigens to antigen-presenting cells. A DNA vaccine may be created through the insertion of single or multiple genes of interest, such as genes for known antigens, into a viral vector such as a poxvirus.
The pox vectors vaccinia and avipoxfowlpox and/or canarypox (ALVAC, Aventis Pasteur)have been used successfully in this regard. These vectors allow for insertion of multiple genes, do not integrate into host DNA, and efficiently infect antigen-presenting cells, including dendritic cells.
According to Dr. Schlom, the use of two different recombinant vectors, known as a prime-and-boost strategy, induces a more potent T-cell response compared with the use of a single vector. Multiple vaccinations with recombinant vaccinia vectors cannot be used because of induction of host immunity to the virus, he said. However, primary vaccination with a recombinant vaccinia vector followed by booster vaccinations with a recombinant avipox vector can optimally induce T-cell responses.