Immune responses to gene therapy are important considerations in the development of effective vectors. In vivo delivery of recombinant adenoviruses have established important principles likely to be relevant to many other systems. Humoral immune responses develop to the capsid proteins of the input virus, which diminish the efficiency of vector readministration. Adenoviruses deleted of the E1 genes express viral proteins in the transduced cell, which activate destructive cytotoxic T lymphocytes (CTLs). Frequently, the transgene product can serve as a target for CTL, as well. Dr. Naren Chirmule was recruited to the Institute for Human Gene Therapy (IHGT) in 1996 to establish a core facility in immunology. This Core provides a large profile of an in vitro assays to measure cellular and humoral immune responses to vectors and transgene products. Included are analyses of CD4+ T cells (lymphoproliferation and cytokine release assays) as well as chromium release assays to assess CTLs. Humoral immune responses are measured through ELISA, Western Blots, isotype fractionation, and neutralizing assays. Viral and transgene products are evaluated as potential antigens in these assays. The Immunology Core provides full service to P30 investigators in areas of basic, translational, and clinical research. The core is a useful mechanism to assure standardization of assays across different protocols.
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