Vaccination of stage IV patients with allogeneic IL-4- or IL-2-gene-transduced melanoma cells generates functional antibodies against vaccinating and autologous melanoma cells.
The antibody (Ab) response to allogeneic Me14932 and autologous melanoma cells was analyzed in 13 Stage IV (AJCC) melanoma patients immunized with Me14932 cells transduced with the IL-4 (Me14932/IL-4) ( n=10) or IL-2 (Me14932/IL-2) ( n=3) gene. No Ab response was observed before the 4th vaccination. Among 8 patients that received four vaccinations, 3/5 patients vaccinated with Me14932/IL-4 cells developed Ab (IgG and/or IgM) to Me14932 ( n=3) and to autologous ( n=2) melanoma cells, and 2/3 patients vaccinated with Me14932/IL-2 cells developed Ab (IgG) to Me14932, but not to autologous melanoma cells. Further, among these 5 responding patients, circulating Ab against the HLA-A3 allele, expressed only on vaccinating cells, were identified in the immune sera of 4 patients immunized with Me14932/IL-4 ( n=2) or Me14932/IL-2 ( n=2) cells. These sera mediated antibody-dependent cell cytotoxicity (ADCC) of Me14932 cells, and a direct correlation ( r=0.85; P=0.03) between intensity of staining (IgG) and extent of lysis was found. Immune serum of one of these patients also induced ADCC of autologous melanoma cells, and serum from another patient mediated complement cytotoxicity of Me14932, but not of autologous melanoma cells. Thus, Abs against vaccinating and autologous melanoma cells were generated in 62% of patients after four vaccinations with cytokine-transduced melanoma cells. These findings demonstrate that the identification and titration of alloreactive Ab helps to monitor the extent of immunization against cellular vaccines, while the induction of Ab reactive to antigens shared between vaccinating and autologous melanoma cells may contribute to their therapeutic efficacy.
Maio
Michele
M
Cancer Bioimmunotherapy Unit and Division of Anesthesia, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico, Via Pedemontana Occ.le, 12, Aviano, 33081 Italy. mmaio@cro.it
Fonsatti
Ester
E
Lamaj
Elda
E
Altomonte
Maresa
M
Cattarossi
Ilaria
I
Santantonio
Cristina
C
Melani
Cecilia
C
Belli
Filiberto
F
Arienti
Flavio
F
Colombo
Mario P
MP
Parmiani
Giorgio
G
D000912:Antibodies, Neoplasm / Q000096:biosynthesis* / Q000276:immunology; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity; D019496:Cancer Vaccines / Q000627:therapeutic use*; D015316:Genetic Therapy; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D007167:Immunotherapy; D007376:Interleukin-2 / Q000235:genetics* / Q000502:physiology; D015847:Interleukin-4 / Q000235:genetics* / Q000502:physiology; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000276:immunology* / Q000637:transplantation; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D014184:Transplantation, Homologous
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D015847:Interleukin-4