Autologous melanoma vaccine induces antitumor and self-reactive immune responses that affect patient survival and depend on MHC class II expression on vaccine cells.
OBJECTIVE
Autologous melanoma cells display a broad variety of tumor antigens and were used for treatment of American Joint Committee on Cancer stages III and IV melanoma as an adjuvant or active therapy. Survival data and immune response were evaluated in vaccinated patients.


METHODS
Forty-seven patients received 2,4-dinitrophenyl-conjugated autologous melanoma vaccine as an adjuvant (23 patients) or therapy (24 patients). CD4 and CD8 T-cell response in blood sampled before vaccination and after five or eight vaccine doses was evaluated against melanoma cells and autologous peripheral blood mononuclear cells using IFNgamma enzyme-linked immunospot. Serum levels of antilivin, an inhibitor of apoptosis, and anti-gp100 IgG were determined.


RESULTS
The immunologic effect of the vaccine differed between the two groups of patients. In the adjuvant group, there was a significant increase in CD8 melanoma-reactive T cells (P = 0.035) after vaccination and an increase in antimelanoma CD4 T cells correlating with improved overall survival (P = 0.04). In the therapeutic group, there was no objective tumor regression; antimelanoma T-cell reactivity increased by a small amount, stayed the same, or in some cases decreased. In all patients, a significant increase was noted in CD4 T-cell reactivity against autologous peripheral blood mononuclear cells (P = 0.02), which did not affect survival. Increased antilivin IgG was associated with improved survival. Expression of MHC class II on melanoma cells was vital for the immunogenicity of the vaccine.


CONCLUSIONS
Autologous melanoma cell vaccine is capable of inducing effective antimelanoma CD4 T-cell activity associated with improved survival. Patients with active metastatic disease generally displayed reduced immune response and gained little from active immunization.
Lotem
Michal
M
Sharett Institute of Oncology and Departments of Surgery, Hadassah Hebrew University Hospital, Ein Karem and Mount Scopus Campuses, Jerusalem, Israel. mlotem@hadassah.org.il
Machlenkin
Arthur
A
Hamburger
Tamar
T
Nissan
Aviram
A
Kadouri
Luna
L
Frankenburg
Shoshana
S
Gimmon
Zvi
Z
Elias
Orit
O
David
Inna Ben
IB
Kuznetz
Anna
A
Shiloni
Eitan
E
Peretz
Tamar
T
D019297:2,4-Dinitrophenol / Q000276:immunology; D048868:Adaptor Proteins, Signal Transducing / Q000097:blood; D015551:Autoimmunity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007167:Immunotherapy; D051034:Inhibitor of Apoptosis Proteins / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000097:blood; D009363:Neoplasm Proteins / Q000097:blood; D012878:Skin Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D058951:gp100 Melanoma Antigen
D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; D019496:Cancer Vaccines; D000949:Histocompatibility Antigens Class II; D051034:Inhibitor of Apoptosis Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen; D007371:Interferon-gamma; D019297:2,4-Dinitrophenol