Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: clinical and immunologic findings.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Belli
Filiberto
F
Unit of General Surgery 2, Istituto Nazionale Tumori, Milan, Italy.
Testori
Alessandro
A
Rivoltini
Licia
L
Maio
Michele
M
Andreola
Giovanna
G
Sertoli
Mario Roberto
MR
Gallino
Gianfrancesco
G
Piris
Adriano
A
Cattelan
Alessandro
A
Lazzari
Ivano
I
Carrabba
Matteo
M
Scita
Giorgio
G
Santantonio
Cristina
C
Pilla
Lorenzo
L
Tragni
Gabrina
G
Lombardo
Claudia
C
Arienti
Flavio
F
Marchianò
Alfonso
A
Queirolo
Paola
P
Bertolini
Francesco
F
Cova
Agata
A
Lamaj
Elda
E
Ascani
Lucio
L
Camerini
Roberto
R
Corsi
Marco
M
Cascinelli
Natale
N
Lewis
Jonathan J
JJ
Srivastava
Pramod
P
Parmiani
Giorgio
G
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007150:Immunohistochemistry; D007167:Immunotherapy; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012074:Remission Induction; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006680:HLA Antigens; D006360:Heat-Shock Proteins