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PMID: 18317358 Published · ppublish English Clinical Trial, Phase I Clinical Trial, Phase II Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Journal of immunotherapy (Hagerstown, Md. : 1997) ·Vol. 31 ·No. 3 ·2008-04-00 ·Pages 294-309

Butterfield LH, Comin-Anduix B, Vujanovic L, Lee Y, Dissette VB, Yang JQ, Vu HT, Seja E, Oseguera DK, Potter DM, Glaspy JA, Economou JS, Ribas A

Abstract

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.

MeSH Terms
Adenoviridae/genetics,immunology Adult Aged Aged, 80 and over Antigens, Neoplasm/chemistry,immunology CD4-Positive T-Lymphocytes/immunology,pathology CD8-Positive T-Lymphocytes/immunology,pathology Cancer Vaccines/immunology,therapeutic use Dendritic Cells/immunology Female Humans Immunodominant Epitopes/immunology Immunotherapy, Active/adverse effects MART-1 Antigen Male Melanoma/immunology,pathology,therapy Middle Aged Neoplasm Metastasis Neoplasm Proteins/chemistry,immunology Neoplasm Staging Protein Engineering Transduction, Genetic Treatment Outcome
Chemicals
Antigens, Neoplasm Cancer Vaccines Immunodominant Epitopes MART-1 Antigen MLANA protein, human Neoplasm Proteins
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Butterfield Lisa H
Department of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA. butterfieldl@upmc.edu
Comin-Anduix Begonya
Vujanovic Lazar
Lee Yohan
Dissette Vivian B
Yang Jin-Quan
Vu Hong T
Seja Elizabeth
Oseguera Denise K
Potter Douglas M
Glaspy John A
Economou James S
Ribas Antoni
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Article Info
Journal
Journal of immunotherapy (Hagerstown, Md. : 1997)
Abbr.
J Immunother
ISSN
1524-9557
DOI
10.1097/CJI.0b013e31816a8910
Email
butterfieldl@upmc.edu
Published
2008-04-00
Pages
294-309
Language
English
Region
United States
NLM ID
9706083
PMCID
PMC3651040
Subset
IM
Grants
NCI NIH HHS · R01 CA079976 · United States
NCI NIH HHS · R01 CA 79976 · United States
External Links
PubMed source DOI: 10.1097/CJI.0b013e31816a8910 PMC Full Text View journal details
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