Development of Antigen Presenting Cells for Adoptive Immunotherapy in Prostate Cancer
Final rept. 1 Dec 2004-30 Nov 2008
JOHNS HOPKINS UNIV BALTIMORE MD
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While adoptive immunotherapy holds promise as a treatment for cancer and infectious diseases, development has been impeded by the lack of reproducible methods for generating therapeutic numbers of antigen-specific CD8 CTL. As a result, there are only limited reports of expansion of antigen-specific CTL to levels required for clinical therapy. Therefore, our groups has previously developed artificial Antigen-Presenting Cells aAPC, made by coupling soluble HLA-Ig and anti-CD28 to beads. These aAPC have successfully been used to induce and expand CTL specific for CMV or melanoma. For the current study we have proposed to used and further developed those aAPC for the generation of prostate cancer specific CTL. Our preliminary data demonstrate that aAPC loaded with the prostate cancer specific antigen EpHA2 have been used to generate functional active prostate cancer-specific CTL from peripheral blood healthy donors. In addition, to overcome the problem of the limited expansion of the prostate cancer specific CTL, we have studied the potential of aAPC to activate and expand antigen specific CTL in vivo. Therefore, we have established an in vivo treatment model of subcutaneous melanoma and demonstrated that aAPC immunization significantly delayed tumor growth.
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