Soluble membrane antigens of human malignant melanoma cells

Hollinshead, Ariel C.; Herberman, Ronald B.; Jaffurs, William J.; Alpert, Louis K.; Minton, John P.; Harris, Jules E.

doi:10.1002/1097-0142(197410)34:4<1235::aid-cncr2820340433>3.0.co;2-k

Cited by 55 publications

(12 citation statements)

References 24 publications

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“…Bodurtha et al (1975), by a complementdependent cytotoxicity assay for antibodies to malignant melanoma, confirmed the findings of Lewis et al (1969). Other investigators, however, have shown crossreactivity with membrane immunofluorescence and cell-mediated assays (Morton et al, 1968;Currie et al, 1971;Nairn et al, 1972;and Hollinshead et al, 1974).…”

Section: Discussionmentioning

confidence: 65%

Anti-tumour immunity in malignant melanoma assay by tube leucocyte adherence inhibition

Marti¹,

Thomson²

1976

Br J Cancer

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Summary.-Tumour antigen-induced inhibition of leucocyte adherence was modified for use in glass test tubes (Tube LAI assay) for the study of cell-mediated antitumour immunity to human malignant melanoma. Peripheral blood leucocytes (PBL) of 20 out of 25 patients (80%) with active malignant melanoma responded to an extract of malignant melanoma with LAI, whereas only 4.5%o of 475 control subjects showed a response. The malignant melanoma patients reacted to both allogeneic and autologous extracts of malignant melanoma which indicates a common cross-reacting antigen. Malignant melanoma patients did not respond to unrelated tumour extracts. The LAI was mediated by PBL (monocytes) " armed" with cytophilic anti-tumour antibody specific for the sensitizing tumour antigen.The anti-tumour response of the malignant melanoma patients was dependent on the stage of the cancer, and 11 out of 13 Stage I patients had a positive NAI, whereas patients with disseminated cancer had decreased response. The diminished LAI in patients with large tumour burdens appeared to be the result of release of tumour antigen systemically. Also, surgery and chemotherapy depressed LAI. Although LAI was depressed after surgical excision of the cutaneous melanoma, most patients showed LAI 1-3 months later. Tumour-free melanoma patients monitored for one year by the Tube LAI assay showed a decline in their anti-tumour immunity 5-6 months after surgery. The NAI was low or negative after the 8th post-surgical month in tumour-free patients. Patients with residual malignant melanoma showed persistent or recurrent LAI after the 8th post-surgical month. LAI reactivity monitored after " curative " surgery for malignant melanoma may assist in determining whether the patient is tumour-free or has a recurrence.

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Section: Discussionmentioning

confidence: 65%

Anti-tumour immunity in malignant melanoma assay by tube leucocyte adherence inhibition

Marti¹,

Thomson²

1976

Br J Cancer

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“…Numerous investigators have reported the existence ofantigens associated with human mammary tumors (1)(2)(3)(4)(5)(6)(7)(8)(9). These studies, all conducted with conventional hyperimmune polyclonal sera, however, were unfortunately hampered with regard to the heterogeneity of the antibody populations employed and the amount of specific immunoglobulin that could be generated.…”

mentioning

confidence: 99%

A spectrum of monoclonal antibodies reactive with human mammary tumor cells.

Colcher¹,

Hand²,

Nuti³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

453

162

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Splenic lymphocytes of mice, immunized with membrane-enriched fractions ofmetastatic human mammary carcinoma tissues, were fused with the NS-1 non-immunoglobulinsecreting murine myeloma cell line. This resulted in the generation of hybridoma cultures secreting immunoglobulins reactive in solid-phase radioimmunoassays with extracts of metastatic mammary carcinoma cells from involved livers, but not with extracts ofapparently normal human liver. As a result offurther screening of immunoglobulin reactivities and double cloning of cultures, 11 monoclonal antibodies were chosen that demonstrated reactivities with human mammary tumor cells and not with apparently normal human tissues. These monoclonal antibodies could be placed into at least five major groups on the basis of their differential binding to the surface of various live human mammary tumor cells in culture, to extracts of mammary tumor tissues, or to tissue sections of mammary tumor cells studied by the immunoperoxidase technique. Whereas a spectrum of reactivities to mammary tumors was observed with the 11 monoclonal antibodies, no reactivity was observed to apparently normal cells of the following human tissues: breast, lymph node, lung, skin, testis, kidney, thymus, bone marrow, spleen, uterus, thyroid, intestine, liver, bladder, tonsils, stomach, prostate, and salivary gland. Several of the antibodies also demonstrated a "pancarcinoma" reactivity, showing binding to selected non-breast carcinomas. None of the monoclonal antibodies showed binding to purified ferritin or carcinoembryonic antigen. Monoclonal antibodies of all five major groups, however, demonstrated binding to human metastatic mammary carcinoma cells both in axillary lymph nodes and at distal sites.Numerous investigators have reported the existence ofantigens associated with human mammary tumors (1-9). These studies, all conducted with conventional hyperimmune polyclonal sera, however, were unfortunately hampered with regard to the heterogeneity of the antibody populations employed and the amount of specific immunoglobulin that could be generated. Since the advent ofhybridoma technology (10), monoclonal antibodies of predefined specificity and virtually unlimited quantity may now be generated against a variety of antigenic determinants present on normal or neoplastic cells. The rationale of the studies reported here was to utilize extracts ofhuman metastatic mammary tumor cells as immunogens in an attempt to generate and characterize monoclonal antibodies reactive with determinants that would be maintained on metastatic, as well as primary, human mammary carcinoma cells. Multiple assays using tumor cell extracts, tissue sections, and live cells in culture have been employed to reveal the diversity of the monoclonal antibodies generated.MATERIALS AND METHODS Immunizations. Membrane-enriched cell extracts were prepared from breast tumor metastases to the liver from two patients as well as from apparently normal liver as described (11) Hybridoma Methodology. Somatic cell hybrids wer...

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“…To Several investigators have presented evidence for the existence of antigens associated with human mammary tumors (1)(2)(3)(4)(5)(6)(7)(8). The studies reported here were undertaken with the hypothesis that B lymphocytes in the axillary lymph nodes of patients with primary breast tumors or in lymph nodes containing metastatic mammary carcinoma cells may already be primed to synthesize antibodies against antigens shed by tumor cells Previous studies have demonstrated that human lymphocyte cells can be fused with murine cells, resulting in cultures that secrete human Igs (9)(10)(11).…”

mentioning

confidence: 99%

Generation of human monoclonal antibodies reactive with human mammary carcinoma cells.

Schlom¹,

Wunderlich²,

Teramoto³

1980

Proc. Natl. Acad. Sci. U.S.A.

214

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Lymphocytes from lymph nodes obtained at mastectomy in breast cancer patients have been fused with murine nonproducer myeloma cells to obtain human-mouse hybridoma cultures that synthesize human monoclonal antibodies. To date, 52 hybridoma cultures synthesizing either human IgG or human IgM have been obtained from lymph nodes of 13 patients. Ig production was stable in many of these cloned cultures through 60-200 days of observation. Levels of human Ig synthesis ranged from 0.1 to 20 microgram/ml of supernatant fluid. The immunological reactivities of the human Igs were assayed on tissue sections by using the immunoperoxidase technique. Several of the human monoclonal antibodies demonstrated preferential binding to human mammary tumor cells. One human IgM monoclonal antibody was used to discriminate between mammary carcinoma cells (from 55 of 59 patients) and normal mammary epithelial cells, stroma, or lymphocytes of the same breast. Decreased binding to some of the benign breast tumors tested and to selected non-breast adenocarcinomas was also observed. This same human monoclonal antibody, however, reacted significantly with metastatic mammary carcinoma cells in lymph nodes of breast cancer patients, with no binding to normal lymphocytes or to stroma of the same node. These studies demonstrate that stable clones of human-mouse hybridomas can be generated by using lymph nodes of mastectomy patients and that clones can be selected which synthesize human monoclonal antibodies reactive with human mammary carcinoma cells.

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Soluble membrane antigens of human malignant melanoma cells

Cited by 55 publications

References 24 publications

Anti-tumour immunity in malignant melanoma assay by tube leucocyte adherence inhibition

Anti-tumour immunity in malignant melanoma assay by tube leucocyte adherence inhibition

A spectrum of monoclonal antibodies reactive with human mammary tumor cells.

Generation of human monoclonal antibodies reactive with human mammary carcinoma cells.

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