Abstract | PURPOSE: EXPERIMENTAL DESIGN: Fifteen patients with high-risk resected stage III and IV melanoma were enrolled. Each patient received peptides + incomplete Freund's adjuvant with SD-9427 at doses of either 10, 20, or 40 microg/kg s.c. for 3 days before and 7 days after each vaccination. Immunizations were administered every month for 6 months and then administered once 6 months later. A leukapheresis to obtain peripheral blood mononuclear cells for immune analyses as well as skin testing with peptides and recall antigens was performed before and after vaccination. IFN- gamma release assay, ELISPOT, and MHC- peptide tetramer analysis were performed using peripheral blood mononuclear cells collected before and after vaccination to evaluate peptide-specific cytotoxic T-cell responses. RESULTS: Local pain and granuloma formation and fatigue of grade I or II were the most common side effects. One patient developed antibody-mediated leukopenia and transient grade III neutropenia that resolved after stopping SD-9427. Six of 12 patients tested developed a positive skin test response to one or more of the peptides. Seven of 10 patients tested demonstrated an immune response to at least one peptide when evaluated by IFN-gamma release assay and ELISPOT assay after vaccination, as did 11 of 12 patients analyzed by MHC- peptide tetramer assay. Four of 15 patients have relapsed with a median follow-up of 20 months, and 1 patient in this high-risk group has died of disease. CONCLUSIONS:
SD-9427 with a multipeptide vaccine was generally well tolerated, although one patient developed reversible antibody-mediated neutropenia. These data suggest that the majority of patients with resected melanoma mount an antigen-specific immune response against a multipeptide vaccine administered with SD-9427.
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Authors | Vinod Pullarkat, Peter P Lee, Ronaldo Scotland, Valerie Rubio, Susan Groshen, Conway Gee, Roy Lau, Jolie Snively, Shirley Sian, Susan L Woulfe, Richard A Wolfe, Jeffrey S Weber |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 9
Issue 4
Pg. 1301-12
(Apr 2003)
ISSN: 1078-0432 [Print] United States |
PMID | 12684398
(Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antigens, Neoplasm
- Cancer Vaccines
- Colony-Stimulating Factors
- Cytokines
- Epitopes
- MART-1 Antigen
- MLANA protein, human
- Membrane Glycoproteins
- Neoplasm Proteins
- PMEL protein, human
- Peptides
- Recombinant Proteins
- Vaccines
- Vaccines, Subunit
- gp100 Melanoma Antigen
- progenipoietin-1
- Monophenol Monooxygenase
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Antigens, Neoplasm
- Cancer Vaccines
(metabolism)
- Colony-Stimulating Factors
(pharmacology, therapeutic use)
- Cytokines
(metabolism)
- Dendritic Cells
(metabolism)
- Epitopes
- Female
- Flow Cytometry
- Humans
- Immunohistochemistry
- Leukapheresis
- MART-1 Antigen
- Male
- Melanoma
(drug therapy, metabolism, surgery)
- Membrane Glycoproteins
(biosynthesis)
- Middle Aged
- Monophenol Monooxygenase
(biosynthesis)
- Neoplasm Proteins
(biosynthesis)
- Peptides
(chemistry)
- Recombinant Proteins
- Time Factors
- Treatment Outcome
- Vaccines
(metabolism)
- Vaccines, Subunit
(metabolism)
- gp100 Melanoma Antigen
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