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

J Immunother 2008 Apr;31(3):294-309

Department of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1097/CJI.0b013e31816a8910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651040PMC
April 2008
27 Reads

Publication Analysis

Top Keywords

t-cell responses
12
metastatic melanoma
12
ifn-gamma elispot
8
responses mart-1
8
autologous dendritic
8
patients received
8
cd4+ cells
8
patients
6
vaccine
6
melanoma
6
measured antigen
4
elispot measured
4
mart-1 51-73
4
vaccine cd4+
4
cd4+ t-cell
4
antigen response
4
51-73 ifn-gamma
4
spreading immunizing
4
antigen mart-1
4
mart-1 melanoma
4

Similar Publications