SEROLOGICAL RESPONSE PATTERNS OF MELANOMA PATIENTS IMMUNIZED WITH A GM2 GANGLIOSIDE CONJUGATE VACCINE

被引:50
作者
KITAMURA, K [1 ]
LIVINGSTON, PO [1 ]
FORTUNATO, SR [1 ]
STOCKERT, E [1 ]
HELLING, F [1 ]
RITTER, G [1 ]
OETTGEN, HF [1 ]
OLD, LJ [1 ]
机构
[1] MEM SLOAN KETTERING CANC CTR,DEPT MED,NEW YORK,NY 10021
关键词
CANCER VACCINE; TUMOR ANTIGEN; GLYCOCONJUGATE; GLYCOLIPID;
D O I
10.1073/pnas.92.7.2805
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Gangliosides, such as GM2, GD2, GD3, and 9-O-acetyl GD3, are receiving attention as targets for antibody-based and vaccine-based therapies of melanoma, GM2 appears to be a particularly immunogenic ganglioside in humans, as indicated by the presence of naturally occurring IgM anti-GM2 antibodies in approximate to 5% of humans and the fact that immunization with irradiated GM2-expressing melanoma cells or purified GM2 adherent to bacillus Calmette-Guerin elicits GM2 antibodies of low to moderate titers in a high proportion of vaccinated patients, To develop vaccines that consistently induce high titers of IgM as well as IgG anti-GM2 antibodies, vaccines containing GM2 conjugated to keyhole limpet hemocyanin as the carrier protein and QS-21 as the adjuvant have been constructed. The serological response of vaccinated patients was monitored by ELISA using purified GM2 ganglioside for IgM and IgG anti-GM2 antibodies and for GM2 cell surface-reactive antibodies by immune adherence assays and cytotoxic tests (IgM antibodies) and mixed hemadsorption assays (IgG antibodies). The majority of vaccinated patients developed IgM and IgG antibodies detectable by ELISA. In most cases, the results of IgM ELISA correlated with assays for cell surface-reactive IgM antibodies. This was not true for IgG anti-GM2 antibodies, where strong discrepancies were seen between high titers in ELISA and little or no reactivity in mixed hemadsorption tests for cell surface-reactive antibodies. These IgG antibodies (and the less frequent IgM antibodies that show similar discrepancies) may be directed against GM2 determinants that are buried, hidden, or not present on GM2-expressing target cells, With regard to a major objective of ganglioside vaccines-i.e., generation of cytotoxic antibodies-the GM2-keyhole limpet hemocyanin/QS-21 vaccine is clearly superior to the previously tested GM2/bacillus Calmette-Guerin vaccine. However, variability in patient response and lack of persistence of high-titered IgM cytotoxic antibodies in many patients are problems that remain to be solved.
引用
收藏
页码:2805 / 2809
页数:5
相关论文
共 39 条
[1]  
CARY TE, 1976, P NATL ACAD SCI USA, V73, P3278
[2]   LOCALIZATION OF THE GANGLIOSIDES GD2 AND GD3 IN ADHESION PLAQUES AND ON THE SURFACE OF HUMAN-MELANOMA CELLS [J].
CHERESH, DA ;
HARPER, JR ;
SCHULZ, G ;
REISFELD, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (18) :5767-5771
[3]   DISIALOGANGLIOSIDE GD3 ON HUMAN-MELANOMA SERVES AS A RELEVANT TARGET ANTIGEN FOR MONOCLONAL ANTIBODY-MEDIATED TUMOR CYTOLYSIS [J].
CHERESH, DA ;
HONSIK, CJ ;
STAFFILENO, LK ;
JUNG, G ;
REISFELD, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (15) :5155-5159
[4]  
CHEUNG NKV, 1985, CANCER RES, V45, P2642
[5]   GANGLIOSIDE GD2 SPECIFIC MONOCLONAL ANTIBODY-3F8 - A PHASE-I STUDY IN PATIENTS WITH NEUROBLASTOMA AND MALIGNANT-MELANOMA [J].
CHEUNG, NKV ;
LAZARUS, H ;
MIRALDI, FD ;
ABRAMOWSKY, CR ;
KALLICK, S ;
SAARINEN, UM ;
SPITZER, T ;
STRANDJORD, SE ;
COCCIA, PF ;
BERGER, NA .
JOURNAL OF CLINICAL ONCOLOGY, 1987, 5 (09) :1430-1440
[6]  
CREEKMORE S, 1992, P AM SOC CLIN ONCOL, V1186, P345
[7]   CELL-SURFACE ANTIGENS OF HUMAN-MALIGNANT MELANOMA - DEFINITION OF 6 ANTIGENIC SYSTEMS WITH MOUSE MONOCLONAL-ANTIBODIES [J].
DIPPOLD, WG ;
LLOYD, KO ;
LI, LTC ;
IKEDA, H ;
OETTGEN, HF ;
OLD, LJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1980, 77 (10) :6114-6118
[8]  
GARINCHESA P, 1989, AM J PATHOL, V134, P295
[9]   GANGLIOSIDE EXPRESSION ON HUMAN-MALIGNANT MELANOMA ASSESSED BY QUANTITATIVE IMMUNE THIN-LAYER CHROMATOGRAPHY [J].
HAMILTON, WB ;
HELLING, F ;
LLOYD, KO ;
LIVINGSTON, PO .
INTERNATIONAL JOURNAL OF CANCER, 1993, 53 (04) :566-573
[10]  
HELING F, 1994, CANCER RES, V54, P197