Immunization with a tumor-cell-lysate-loaded autologous-antigen-presenting-cell-based vaccine in melanoma.
The discoveries of human melanoma-associated antigens in molecular terms have renewed interest in peptide- or peptide- and antigen-presenting-cell (APC)-based cancer vaccines. Considering the limited scope of immunization using defined peptides, we have studied an alternative approach of specific immunization with tumor-lysate-loaded autologous APC (adherent peripheral mononuclear cells cultured in 1000 U granulocyte/macrophage-colony-stimulating factor for 14 days) as a surrogate vaccine. Seventeen patients (11 with active metastatic disease) were intradermally immunized with the vaccine in a phased dose escalation (10(5)-10(7) cells/injection) monthly for 4 months. Thirteen patients completed all four immunizations showing no toxicity (3 patients had to be taken off study because of progressive disease and 1 patient went off study as a result of myocardial infarction due to multi-vessel coronary artery disease). None has shown any immediate or delayed toxicity attributable to the immunization and none has shown any evidence of autoimmunity. One patient showed a partial regression of a subcutaneous nodule. Thirteen patients are alive after 4+ months to 30+ months (17-month median survival for the group). Nine patients showed evidence of delayed-type hypersensitivity at the vaccine sites. Monitoring of biological response in conventional natural killer or cytolytic T lymphocyte assays with pre- and post-immune peripheral blood lymphocytes revealed no consistent differences. The vaccine-infiltrating lymphocytes (VIL) from nine specimens were adequately expanded following in vitro stimulation with the respective autologous-lysate-loaded APC for phenotypic and functional analyses. Five of the nine ex vivo expanded VIL were predominantly CD8+. Evidence of an antigen-specific CD8+ T cell response (cytotoxicity and/or tumor necrosis factor production) was detected in three of the five CD8+ VIL. These observations suggest that this type of vaccine is feasible, that it has biological activity, and that the approach may be improved through additional strategic manipulations.
Chakraborty
N G
NG
Department of Medicine, University of Connecticut School of Medicine, Farmington 06030, USA.
Sporn
J R
JR
Tortora
A F
AF
Kurtzman
S H
SH
Yamase
H
H
Ergin
M T
MT
Mukherji
B
B
D000917:Antibody Formation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use / Q000633:toxicity; D005260:Female; D006801:Humans; D016233:Immunotherapy, Active; D008297:Male; D008545:Melanoma / Q000628:therapy*; D014611:Vaccination / Q000009:adverse effects
D019496:Cancer Vaccines