AACR/NCI/EORTC, 2001
Abstract #799

Vaccination with autologous heat-shock protein peptide complex-96 (HSPPC-96, Oncophage) in metastatic melanoma

G Parmiani, F Belli, A Testori, M Maio, MR Sertoli, G Andreola, G Gallino, A Piris, R Camerini, JJ Lewis, PK Srivastava, L Rivoltini, Inst Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy; Inst Europeo di Oncologia, Milano, Italy; Ctr Riferimento Oncologico, Aviano, Italy; Inst Tumori Genova, Genova, Italy; Sigma Tau, Roma, Italy; Antigenics, New York, NY; Univ of Connecticut School of Medicine, Farmington, CT.

Heat shock proteins isolated from mouse tumors have been shown to elicit tumor immunity against individual but not unrelated tumors. We vaccinated 45 metastatic (AJCC stage IV) melanoma patients with HSPPC-96. Eleven patients were rendered disease-free after surgery, whereas 28 were left with measurable disease after resection for tumor procurement and vaccine production. Patients received 5 µg or 50 µg of HSPPC-96 once weekly x 4. After a 4-week interval, some patients received 4 additional vaccinations. No grade III or IV toxicities were noted. Two complete responses (CRs) and 3 long-term stable diseases (SDs) were observed among the 28 patients with measurable disease. Duration of CRs was 559+ and 703+ days, and SDs lasted for 153, 191 and 272 days, respectively. Among the 11 patients made disease-free, disease-free survival (DFS) ranged from 1 to 601+ days (median DFS = 94 days). Immunological monitoring was carried out by in vitro ELISPOT (IFN-g) assay in 23 patients. A significant increase in the number of post-vaccination, melanoma-specific T-cell spots was evident in 11 cases (47.8%), with clinical responders showing a higher frequency of T-cell response. Tetramers HLA-A2/MART1 staining of T cells showed increased frequency of anti-MART1 T cells in 3 clinical responders, but not in non-responders. Pathological analysis of 18 tumor lesions from which vaccine was produced revealed 11 cases of HLA class I downregulation, whereas MART-1 or gp100 antigens were downregulated in 5 and 6 cases, respectively. However, tumors of 5/6 clinical responders (including 2 CRs and 3 SDs), but only of 3/13 non-responders, displayed high expression of both class I HLA and melanoma antigens. These results indicate that vaccination of metastatic melanoma patients with HSPPC-96 is feasible, devoid of significant toxicity and can induce clinical responses that appear to be associated with a melanoma-specific, T cell-mediated immune reaction.