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193 Dendritic Cell-Based Vaccine/Immunotherapy for HIV
A. Gruber*1, K. L. Kuhen1,3, J. C. Wheat1, D. J. Looney1,2, I. Chen1,3, M. Ibanez1, P. Law1, and F. Wong-Staal1
1Univ. of California, San Diego, USA; 2VA Med. Ctr., La Jolla, CA, USA; and 3Genomics Inst. for the Novartis Res. Fndn., San Diego, CA, USA
Background: The aim of our studies is to develop vaccines/immunotherapies for malignancies and diseases including HIV.
Methods: In a first study we investigated the use of replication-incompetent lentiviral vectors based on HIV-1 for dendritic cell-based vaccine/immunotherapy for HIV/AIDS. The vaccine consists of dendritic cells (DC) derived from monocytes (M-DC) and genetically modified by gene therapeutic vectors.
Results: As an alternative to M-DC we investigated the potential use of CD34+ stem cell-derived DC (CD34-DC) in HIV immunotherapy. CD34-DC from HIV-infected subjects could be transduced with the HIV-based immunotherapeutic vector without affecting their ability to differentiate into functional DC. The latter findings may be important since CD34-DC are superior to M-DC in inducing antigen-specific CTL which, in turn, have been shown to be critical for the control of HIV replication. To determine the feasibility of a DC-based immunotherapy for HIV/AIDS, we investigated further the effect of HIV infection as well as of antiretroviral therapy on DC immunophenotype and function. We found that DC from HIV-infected individuals are hyperresponsive to inflammatory stimuli, and that some HIV-1 protease inhibitors affect DC function.
Conclusions: CD34-DC might be an alternative or addition to M-DC-based immunotherapy for HIV. Suppression of viral replication might be critical for the success of an immunotherapy for HIV/AIDS. Some HIV-1 protease inhibitors, while suppressing viral replication, might affect DC-based immunotherapies. Currently we are testing the safety and efficacy of the above-mentioned vaccine/immunotherapy for HIV, based on dendritic cells and lentiviral vectors, in mice.
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