Article

Cancer Immunity, Vol. 9, p. 5 (5 June 2009) Submitted: 23 March 2009. Accepted: 22 May 2009.

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

Jianda Yuan1*, Geoffrey Y. Ku1*, Humilidad F. Gallardo1, Francesca Orlandi1, Gregor Manukian1, Teresa S. Rasalan1, Yinyan Xu1, Hao Li1, Shachi Vyas1, Zhenyu Mu1, Paul B. Chapman2, Susan E. Krown2, Katherine Panageas3, Stephanie L. Terzulli1, Lloyd J. Old4, Alan N. Houghton1,2 and Jedd D. Wolchok1,2

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

2Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

3Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

4Ludwig Institute for Cancer Research, New York Branch, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

*These authors contributed equally to this work

Communicated by: A Knuth

Keywords: phase I clinical trial, melanoma, gp100, DNA vaccine, cellular immunity

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 µg) 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 gp100280-288 HLA-A2-restricted tetramer. One patient had an increase in CD8+ IFN-γ+ cells. This xenogeneic immunization strategy was safe and associated with minimal toxicity. There was also evidence of immune response.