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Butterfield, L.H. et al.

Lisa H. Butterfield, Begonya Comin-Anduix, Lazar Vujanovic, Yohan Lee, Vivian B. Dissette, Jin-Quan Yang, Hong T. Vu, Elizabeth Seja, Denise K. Oseguera, Douglas M. Potter, John A. Glaspy, James S. Economou, Antoni Ribas,

Adenovirus MART-1-engineered autologous dendritic cell vaccine for metastatic melanoma.

We performed a phase 1/2 trial testing the safety, toxicity, and immune response of a vaccine consisting of autologous dendritic cells (DCs) transduced with a replication-defective adenovirus (AdV) encoding the full-length melanoma antigen MART-1/Melan-A (MART-1). This vaccine was designed to activate MART-1-specific CD+8 and CD4+ T cells. Metastatic melanoma patients received 3 injections of 10(6) or 10(7) DCs, delivered intradermally. Cell surface phenotype and cytokine production of the DCs used for the vaccines were tested, and indicated intermediate maturity. CD8+ T-cell responses to MART-1 27-35 were assessed by both major histocompatibility complex class I tetramer and interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) before, during, and after each vaccine and CD4+ T-cell responses to MART-1 51-73 were followed by IFN-gamma ELISPOT. We also measured antigen response breadth. Determinant spreading from the immunizing antigen MART-1 to other melanoma antigens [gp100, tyrosinase, human melanoma antigen-A3 (MAGE-A3)] was assessed by IFN-gamma ELISPOT. Twenty-three patients were enrolled and 14 patients received all 3 scheduled DC vaccines. Significant CD8+ and/or CD4+ MART-1-specific T-cell responses were observed in 6/11 and 2/4 patients evaluated, respectively, indicating that the E1-deleted adenovirus encoding the cDNA for MART-1/Melan-A (AdVMART1)/DC vaccine activated both helper and killer T cells in vivo. Responses in CD8+ and CD4+ T cells to additional antigens were noted in 2 patients. The AdVMART1-transduced DC vaccine was safe and immunogenic in patients with metastatic melanoma.[1]

References

Adenovirus MART-1-engineered autologous dendritic cell vaccine for metastatic melanoma. Butterfield, L.H., Comin-Anduix, B., Vujanovic, L., Lee, Y., Dissette, V.B., Yang, J.Q., Vu, H.T., Seja, E., Oseguera, D.K., Potter, D.M., Glaspy, J.A., Economou, J.S., Ribas, A. J. Immunother. (2008) [Pubmed]

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