Abstract

To identify antigens in malignant melanoma cells recognized by the free antibodies in human sera and those hidden in soluble immune complexes, we prepared electrophoretic transblots of tumor cell proteins fractionated by electrophoresis in polyacrylamide gels in the presence of detergent. These new methods facilitated the identification of a 30 kilodalton antigen in extracts of the CAR-2 malignant melanoma cell that is recognized preferentially by sera of patients with this disease. Additional studies of the monoclonal antibody-defined melanoma-associated 100 kilodalton antigen demonstrated that high levels of this antigen were present in sera of patients with stage III and IV disease. In sera, the 100 kilodalton antigen forms complexes with albumin, not immunoglobulin. Further studies of the circulating complexes in human sera revealed that these are frequently rich in antibodies specific for Fab' fragments of IgG and may be the circulating residue of ongoing idiotype-anti-idiotype interactions within the humoral limb of the immune system. These naturally occurring anti-immunoglobulins were shown to have a suppressive influence on antibody biosynthesis by pokeweed mitogen-stimulated, human peripheral blood lymphocytes. (IS)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA020543-09
Application #
3165329
Study Section
Experimental Immunology Study Section (EI)
Project Start
1976-09-30
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
9
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

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Schantz, S P; Savage, H E; Racz, T et al. (1989) Immunologic determinants of head and neck cancer response to induction chemotherapy. J Clin Oncol 7:857-64
Jones, M M; Seilheimer, D K; Pollack, M S et al. (1989) Relationship of hypergammaglobulinemia, circulating immune complexes, and histocompatibility antigen profiles in patients with cystic fibrosis. Am Rev Respir Dis 140:1636-9
Kagiyama, A; Savage, H E; Michael, L H et al. (1989) Molecular basis of complement activation in ischemic myocardium: identification of specific molecules of mitochondrial origin that bind human C1q and fix complement. Circ Res 64:607-15
Rossen, R D; Michael, L H; Kagiyama, A et al. (1988) Mechanism of complement activation after coronary artery occlusion: evidence that myocardial ischemia in dogs causes release of constituents of myocardial subcellular origin that complex with human C1q in vivo. Circ Res 62:572-84
Schantz, S P; Savage, H E; Brown, B W et al. (1988) Association of levels of circulating C1q binding macromolecules with induction chemotherapy response in head and neck cancer patients. Cancer Res 48:5868-73
Orson, F M; Flagge, F P; Cashaw, J L (1986) T cell replacing factor for steroids (TRF-S): a 40,000 dalton protein produced by a T4+ T cell. J Immunol 137:578-84
Savage, H E; Rossen, R D; Hersh, E M et al. (1986) Antibody development to viral and allogeneic tumor cell-associated antigens in patients with malignant melanoma and ovarian carcinoma treated with lysates of virus-infected tumor cells. Cancer Res 46:2127-33
Rossen, R D; Laughter, A H; Orson, F M et al. (1985) Human peripheral blood monocytes release a 30,000 dalton factor (30 KD MF) that stimulates immunoglobulin production by activated B cells. J Immunol 135:3289-97