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Cancer Immun. 2009 Jun 5;9:5.

Safety and immunogenicity of a human and mouse gp100 DNA vaccine in a phase I trial of patients with melanoma.

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  • 1Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering Institute, New York, NY, USA.

Abstract

A differentiation antigen commonly expressed on melanoma cells, gp100 is the target of infiltrating T cells. We conducted a phase I randomized cross-over trial of melanoma patients with either xenogeneic (mouse) or human gp100 plasmid DNA injected intramuscularly at three dosages (100, 500 or 1,500 microg) every three weeks for three doses. After the first three injections, patients were then immunized three times with gp100 from the other species. Peripheral blood samples were analyzed at various time points following 10-day culture with gp100 peptides using multi-parametric flow cytometry. A total of 19 patients were enrolled, with 18 assessable for immune function and survival. 14 (74%) were male, with a median age of 56 years (range, 20-82). All patients had no evidence of disease; 10 (53%) had stage III disease, 3 each (16%) had stage IIB and IV disease, 2 (11%) had choroidal and 1 (5%) had anal mucosal involvement. With a median follow-up of 30 months, median progression-free survival (PFS) is 44 months. Median survival is not reached. There was no grade 3/4 toxicity; the most common grade 1/2 toxicity was an injection site reaction in 12 patients (63%, all grade 1). Five patients developed CD8+ cells binding gp100(280-288) HLA-A2-restricted tetramer. One patient had an increase in CD8+ IFN-gamma+ cells. This xenogeneic immunization strategy was safe and associated with minimal toxicity. There was also evidence of immune response.

PMID:
19496531
[PubMed - indexed for MEDLINE]
PMCID:
PMC2888533
Free PMC Article

Images from this publication.See all images (7)Free text

Figure 5;  Polyfunctional cytokine responses following gp100 DNA vaccination.
Table 2
Figure 1;  Change in gp100280-288 HLA*A201-restricted tetramer CD8+ cells following mouse and human gp100 DNA vaccination.
Figure 2;  Changes in (A) gp100280-288 and (B) gp100209-217 HLA*A201-restricted tetramer CD8+ cells following mouse and human gp100 DNA vaccination.
Figure 3;  CCR7, CD45RA, CD27 and CD28 subpopulations in gp100280-288 HLA*A201-restricted tetramer CD8+ cells following mouse and human gp100 DNA vaccination.
Figure 4;  Intracellular cytokine staining (ICS) of patient PBMCs following gp100 DNA vaccination.
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