TY - JOUR
T1 - Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes
T2 - Clinical and immunologic findings
AU - Belli, Filiberto
AU - Testori, Alessandro
AU - Rivoltini, Licia
AU - Maio, Michele
AU - Andreola, Giovanna
AU - Sertoli, Mario Roberto
AU - Gallino, Gianfrancesco
AU - Piris, Adriano
AU - Cattelan, Alessandro
AU - Lazzari, Ivano
AU - Carrabba, Matteo
AU - Scita, Giorgio
AU - Santantonio, Cristina
AU - Pilla, Lorenzo
AU - Tragni, Gabrina
AU - Lombardo, Claudia
AU - Arienti, Flavio
AU - Marchianò, Alfonso
AU - Queirolo, Paola
AU - Bertolini, Francesco
AU - Cova, Agata
AU - Lamaj, Elda
AU - Ascani, Lucio
AU - Camerini, Roberto
AU - Corsi, Marco
AU - Cascinelli, Natale
AU - Lewis, Jonathan J.
AU - Srivastava, Pramod
AU - Parmiani, Giorgio
PY - 2002/10/15
Y1 - 2002/10/15
N2 - Purpose: To determine the immunogenicity and antitumor activity of a vaccine consisting of autologous, tumor-derived heat shock protein gp96-peptide complexes (HSPPC-96, Oncophage; Antigenics, Inc, Woburn, MA) in metastatic (American Joint Committee on Cancer stage IV) melanoma patients. Patients and Methods: Sixty-four patients had surgical resection of metastatic tissue required for vaccine production, 42 patients were able to receive the vaccine, and 39 were assessable after one cycle of vaccination (four weekly injections). In 21 patients, a second cycle (four biweekly injections) was given because no progression occurred. Antigen-specific antimelanoma T-cell response was assessed by enzyme-linked immunospot (ELISPOT) assay on peripheral blood mononuclear cells (PBMCs) obtained before and after vaccination. Immunohistochemical analyses of tumor tissues were also performed. Results: No treatment-related toxicity was observed. Of 28 patients with measurable disease, two had a complete response (CR) and three had stable disease (SD) at the end of follow-up. Duration of CR was 559+ and 703+ days, whereas SD lasted for 153, 191, and 272 days, respectively. ELISPOT assay with PBMCs of 23 subjects showed a significantly increased number of postvaccination melanoma-specific T-cell spots in 11 patients, with clinical responders displaying a high frequency of increased T-cell activity. Immunohistochemical staining of melanoma tissues from which vaccine was produced revealed high expression of both HLA class I and melanoma antigens in seven of eight clinical responders (two with CR, three with SD, and the three with long-term disease-free survival) and in four of 12 nonresponders. Conclusion: Vaccination of metastatic melanoma patients with autologous HSPPC-96 is feasible and devoid of significant toxicity. This vaccine induced clinical and tumor-specific T-cell responses in a significant minority of patients.
AB - Purpose: To determine the immunogenicity and antitumor activity of a vaccine consisting of autologous, tumor-derived heat shock protein gp96-peptide complexes (HSPPC-96, Oncophage; Antigenics, Inc, Woburn, MA) in metastatic (American Joint Committee on Cancer stage IV) melanoma patients. Patients and Methods: Sixty-four patients had surgical resection of metastatic tissue required for vaccine production, 42 patients were able to receive the vaccine, and 39 were assessable after one cycle of vaccination (four weekly injections). In 21 patients, a second cycle (four biweekly injections) was given because no progression occurred. Antigen-specific antimelanoma T-cell response was assessed by enzyme-linked immunospot (ELISPOT) assay on peripheral blood mononuclear cells (PBMCs) obtained before and after vaccination. Immunohistochemical analyses of tumor tissues were also performed. Results: No treatment-related toxicity was observed. Of 28 patients with measurable disease, two had a complete response (CR) and three had stable disease (SD) at the end of follow-up. Duration of CR was 559+ and 703+ days, whereas SD lasted for 153, 191, and 272 days, respectively. ELISPOT assay with PBMCs of 23 subjects showed a significantly increased number of postvaccination melanoma-specific T-cell spots in 11 patients, with clinical responders displaying a high frequency of increased T-cell activity. Immunohistochemical staining of melanoma tissues from which vaccine was produced revealed high expression of both HLA class I and melanoma antigens in seven of eight clinical responders (two with CR, three with SD, and the three with long-term disease-free survival) and in four of 12 nonresponders. Conclusion: Vaccination of metastatic melanoma patients with autologous HSPPC-96 is feasible and devoid of significant toxicity. This vaccine induced clinical and tumor-specific T-cell responses in a significant minority of patients.
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U2 - 10.1200/JCO.2002.09.134
DO - 10.1200/JCO.2002.09.134
M3 - Article
C2 - 12377960
AN - SCOPUS:0037108696
VL - 20
SP - 4169
EP - 4180
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 20
ER -