The rationale for developing immunization protocols which would favor the generation of cellular immune responses is based on the recent realization that a cellular response is elicited when the antigen is expressed from within the antigen presenting cell. Consequently, introduction of the gene encoding the antigen into APC, rather than administering the antigen itself in any other form, may constitute the appropriate or best strategy to elicit a strong and therapeutically useful cellular immune response. Two basic strategies to elicit and amplify cellular immune responses via gene transfer will be studied: a) Ex vivo amplification of a pre-existing cellular response by in vitro stimulation of T-lymphocytes with autologous APC transduced with """"""""antigenic"""""""" foreign genes. This strategy may be applicable to post bone marrow transplant patients at risk of CMV infection or HIV seropositive asymptomatic individuals. b) In vivo immunization, via gene transfer into APC which persist in the individual for extended periods of time. This approach may be used to amplify pre-existing cellular responses,or to generate a primary response in a naive individual. An effective gene transfer system to deliver the antigenic gene at high efficiency into the appropriate APC is a central component in the development of such immunization strategies. Due to histocompatibility restrictions, when dealing with outbred species efficient gene transfer has to be accomplished into autologous cells, which, in general, have a limited capacity to propagate in vitro. Retroviral-based gene transfer, which is one of several gene transfer systems that can be considered for this purpose, possesses several unique features that makes it suitable to develop immunization protocols based on gene transfer.
| Fetten, J V; Roy, N; Gilboa, E (1991) A frameshift mutation at the NH2 terminus of the nucleoprotein gene does not affect generation of cytotoxic T lymphocyte epitopes. J Immunol 147:2697-705 |
