PMID- 12377960 OWN - NLM STAT- MEDLINE DCOM- 20021024 LR - 20161102 IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 20 IP - 20 DP - 2002 Oct 15 TI - Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: clinical and immunologic findings. PG - 4169-80 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. FAU - Belli, Filiberto AU - Belli F AD - Unit of General Surgery 2, Istituto Nazionale Tumori, Milan, Italy. FAU - Testori, Alessandro AU - Testori A FAU - Rivoltini, Licia AU - Rivoltini L FAU - Maio, Michele AU - Maio M FAU - Andreola, Giovanna AU - Andreola G FAU - Sertoli, Mario Roberto AU - Sertoli MR FAU - Gallino, Gianfrancesco AU - Gallino G FAU - Piris, Adriano AU - Piris A FAU - Cattelan, Alessandro AU - Cattelan A FAU - Lazzari, Ivano AU - Lazzari I FAU - Carrabba, Matteo AU - Carrabba M FAU - Scita, Giorgio AU - Scita G FAU - Santantonio, Cristina AU - Santantonio C FAU - Pilla, Lorenzo AU - Pilla L FAU - Tragni, Gabrina AU - Tragni G FAU - Lombardo, Claudia AU - Lombardo C FAU - Arienti, Flavio AU - Arienti F FAU - Marchiano, Alfonso AU - Marchiano A FAU - Queirolo, Paola AU - Queirolo P FAU - Bertolini, Francesco AU - Bertolini F FAU - Cova, Agata AU - Cova A FAU - Lamaj, Elda AU - Lamaj E FAU - Ascani, Lucio AU - Ascani L FAU - Camerini, Roberto AU - Camerini R FAU - Corsi, Marco AU - Corsi M FAU - Cascinelli, Natale AU - Cascinelli N FAU - Lewis, Jonathan J AU - Lewis JJ FAU - Srivastava, Pramod AU - Srivastava P FAU - Parmiani, Giorgio AU - Parmiani G LA - eng GR - 84479/PHS HHS/United States PT - Clinical Trial PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Antigens, Neoplasm) RN - 0 (Cancer Vaccines) RN - 0 (HLA Antigens) RN - 0 (Heat-Shock Proteins) SB - IM EIN - J Clin Oncol 2002 Dec 1;20(23):4610 CIN - J Clin Oncol. 2002 Oct 15;20(20):4139-40. PMID: 12377956 MH - Adult MH - Aged MH - Antigens, Neoplasm/immunology MH - Cancer Vaccines/*immunology/*therapeutic use MH - Female MH - HLA Antigens/*immunology MH - Heat-Shock Proteins/*immunology MH - Humans MH - Immunoassay/methods MH - Immunohistochemistry MH - *Immunotherapy MH - Male MH - Melanoma/immunology/pathology/*therapy MH - Middle Aged MH - Neoplasm Metastasis MH - Remission Induction MH - Skin Neoplasms/immunology/pathology/*therapy MH - Survival Analysis MH - T-Lymphocytes/immunology EDAT- 2002/10/16 04:00 MHDA- 2002/10/31 04:00 CRDT- 2002/10/16 04:00 PHST- 2002/10/16 04:00 [pubmed] PHST- 2002/10/31 04:00 [medline] PHST- 2002/10/16 04:00 [entrez] AID - 10.1200/JCO.2002.09.134 [doi] PST - ppublish SO - J Clin Oncol. 2002 Oct 15;20(20):4169-80. doi: 10.1200/JCO.2002.09.134.