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M R Price

Publications and source records attributed to M R Price.

At least 145 records · Page 8Linked to original sources

Complement-dependent cytotoxicity of anti-human osteogenic sarcoma monoclonal antibodies.

Two mouse monoclonal antibodies against the human osteogenic sarcoma 791T were examined for their capacity to exert complement-dependent cytotoxicity against a panel of human tumour cell lines. Cytotoxicity was most evident against the immunizing tumour 791T although significant reactivity was directed against other osteogenic sarcomas. In admixture, the 2 antibodies displayed synergism in their cytotoxicity although this was only demonstrable with defined ranges of antibody concentration. The cytotoxicity of these antibodies was dependent upon the use of rabbit serum as complement and no tumour-cell lysis was produced using human, guinea-pig or mouse serum complement. The more potent cytotoxic antibody failed to modify the outgrowth of 791T tumour xenografts in immunodeprived mice even though localization of antibody at the tumour site has been demonstrated (Pimm et al., 1982).

Animals↗

Levels of circulating immune complexes in patients with ovarian cancer.

Sera from patients with ovarian tumours were assayed for circulating immune complexes (CIC) by four well established assays based on the interaction of immune complexes with components of the complement system. There was no difference in control, pre- or post-operative or BCG-treated patients' sera. Levels were also unchanged in sera in antigen excess. In patients with ovarian tumours therefore the measurement of CIC would appear to be of little value as a screening test, as a guide to the extent of disease, prognosis or therapy. In a small pilot therapy-trial there was no difference in the survival rate between patients with stage III and IV ovarian cancer treated with cyclophosphamide plus BCG and those who received only cyclophosphamide. Treatment with BCG was associated with postoperative pyrexia and a prolonged hospital stay.

Antigen-Antibody Complex↗

Isolation of a variant of Candida albicans.

During the course of Candida albicans antigen production, a variant of this organism was encountered which did not produce hyphae at 37 degrees C. Presented here are some of the characteristics of this variant. It produces hyphae at 25 degrees C on cornmeal agar and synthetic medium plus N-acetylglucosamine and Tween 80. At 37 degrees C, it does not produce hyphae on these media, although C. albicans normally does produce hyphae under these circumstances. In liquid synthetic medium, this variant does not produce hyphae at 37 degrees C. The variant strain was analyzed for DNA, RNA, protein content, and particle size. After 50 to 70 h in balanced exponential-phase growth, particle size distribution was narrow, and there were no differences in the DNA, RNA, or protein content per particle in the two strains. When balanced exponential-phase cultures were brought into stationary phase, both strains contained the same amount of DNA per cell.

Candida albicans↗

Characteristics of two anti-tumour monoclonal antibody preparations.

Monoclonal antibodies directed against one spontaneously arising rat mammary carcinoma and a human osteogenic sarcoma have been prepared following the fusion of spleen cells from appropriately immunised donors with mouse myeloma cells. The characteristics of these antibodies have been analysed and methods for their purification have been developed using immunoadsorption chromatography or by utilising their affinity for Sepharose-linked Protein A. The use of these antibodies for the identification, characterisation and isolation of their target tumour antigenic structures is described.

Animals↗

Tumour markers with unknown functions in gynaecological neoplasia.

Pre- and post-operative ovarian cancer patients' sera were examined for the presence or circulating immune complexes using a variety of assay procedures. In contrast to findings with breast cancer patients' sera, sera from patients with other gynaecological tumours or with preclinical disease diagnosed by cytology, no evidence was obtained to indicate that circulating immune complexes were associated with ovarian cancer.

Antigen-Antibody Complex↗

Radioiodination of rat hepatoma-specific antigens and retention of serological reactivity.

Papain-solubilized tumour-specific antigens from the aminoazo dye-induced rat hepatoma D23 were purified by a combination of lectin affinity and immunoadsorbent column chromatography. Isolated antigens were radio-iodinated using three procedures and analysed for their reaction with specific antibodies in syngeneic immune sera by double-antibody co-precipitation tests and by the rebinding of labelled antigens to specific and non-relevant antibodies immobilized on Sepharose-4B. Soluble hepatoma D23-specific antigens were labile to radiolabelling, and for optimal retention of serological reactivity it was necessary to protect the antigenic determinant by performing the chloramine T method of iodination with antigen bound to the immunoadsorbent followed by elution from the solid phase with 3M NaSCN. Immunoadsorption chromatography indicated that one consequence of radiolabelling hepatoma D23-specific antigen with 125I was a reduction in the affinity of the labelled antigen for its syngeneic specific antibody.

Animals↗

Organ-related and malignancy-associated reactivity of cancer patients' leucocytes: a leucocyte migration study with tumour and foetal extracts.

Leucocytes from patients with a variety of tumours including gastric, colorectal, lung, kidney and mammary cancer, were tested in the leucocyte migration test (LMT) against organ-related and non-organ-related tumour and foetal extracts. The reactivity of cancer patients' leucocytes against a panel of organ-related tumour extracts was found to be 71-93%, depending on the tumour system tested. Cross-reactivity with a panel on non-organ-related tumour extracts was found in 0-38% of patients. Corresponding patterns of reactivity were obtained by testing patients' leucocytes against human foetal organ extracts; pathological migration indices (MI) were found in 70% of tests in which patients' leucocytes were reacted with organ-related extracts, and in 16% of tests with non-organ-related extracts. The data strongly support the concept that patients' leucocytes are sensitized to cross-reactive foetal determinants of organ-related specificities. Furthermore, it is proposed that foetal extracts as inducers of lymphokine production in presensitized lymphocytes could be used efficiently and reproducibly as a source of foetal antigen, as well as in the clinical application of the LMT procedure.

Adult↗

Lack of correlation between carcinoembryonic antigen content of tumor extracts and leukocyte migration reactivity of tumor patients.

Tumor extracts varying in carcinoembryonic antigen (CEA) content (0.4--2,280 ng/mg protein) did not affect the reactivity of cancer patients' leukocytes in the leukocyte migration inhibition test (LMIT). In addition, variations in the plasma CEA levels of tumor-bearing leukocyte donors did not influence the frequency of significant LMIT reactivity.

Adenocarcinoma↗

Modification of the immunogenicity and antigenicity of rat hepatoma cells. I. Cell-surface stabilization with glutaraldehyde.

gamma-Irradiated rat hepatoma cells are immunogenic in syngeneic WAB/Not rats, so that immunized animals are protected against tumour-cell challenge and circulating tumour-specific antibody is produced. Treatment of the immunizing cells with glutaraldehyde at concentrations of 0.001% or greater for 30 min rendered these cells non-protective in tumour-rejection tests and no longer able to induce significant formation of specific antibody. However, tumour-specific antigens were shown to be expressed upon treated cells; they specifically bound tumour-specific antibody from syngeneic immune sera assessed in indirect membrane-immunofluorescence tests. Also, these cells specifically absorbed antibody from immune or tumour-bearer sera, as demonstrated in the indirect membrane-immunofluorescence test or a complement-dependent 51Cr-release test. Alloantigen expression was not influenced by glutaraldehyde treatment, although glutaraldehyde-treated hepatoma cells failed to induce alloantibody formation in KX/Not rats. Polyacrylamide-gel electrophoresis of treated cells, surface-labelled with 125I, indicated that extensive cross-linking of the surface protein occurred as a result of glutaraldehyde treatment. The present findings establish that although the expression of a tumour-specific antigen is necessary for the induction of immuno-protection against tumour-cell challenge, this alone is not a sufficient condition for eliciting tumour immunity.

Animals↗

Modification of the immunogenicity and antigenicity of rat hepatoma cells. II. Mild heat treatment.

I.p. immunization with gamma-irradiated hepatoma cells induces resistance to s.c. tumour-cell challenge in syngeneic WAB/Not rats. Mild heat treatment of these cells (greater than 41 degrees C for 30 min) destroyed this immunoprotective effect, but did not abolish tumour-specific antibody production in treated rats. The binding of syngeneic and alloantibodies to surface antigens expressed on hepatoma cells was unaffected by heat treatment. Thus, heat-treated gamma-irradiated hepatoma cells retain a serologically defined tumour-specific antigen but are unable to elicit immunoprotection. By examining the incorporation of radioactive precursors into DNA, RNA and protein in heat-treated cells, it was determined that above 41 degrees C there was a significant decrease in metabolic activity. It is postulated that for the effective induction of transplantation immunity to tumours, tumour-specific antigens should be present on the surface membranes of a metabolically active cell. This hypothesis accounts for the absence or marked reduction of immunoprotection induced by inviable or glutaraldehyde-treated cells, isolated cell membranes and soluble tumour extracts which retain serologically defined tumour-specific antigens.

Animals↗

Activity of syngeneic complement for revealing antibody-induced cytotoxicity against a rat hepatoma.

The cytotoxicity of tumour-bearer serum against a transplanted aminoazodye-induced rat hepatoma was revealed using normal rat serum as the source of complement as assessed using a short-term 51Cr release test. The tumour-bearing rat was not deficient in a functional complement system and direct cytolysis against hepatoma cells was demonstrated following admixture of tumour cells and serum with no additional complement. No tumour growth was observed in animals receiving subcutaneous transfer of cells treated with tumour-bearer serum, although when heat-inactivated (56 C for 60 min) or normal sera were used, there was no modification of tumour development. The present findings indicate that the tumour-bearing animal contains both antibodies and complement sufficient for tumour lysis, although the full contribution of serum-mediated cytotoxicity in imposing immunological constraints upon tumour growth remains to be elucidated.

Animals↗

Sensitization of leukocytes of cancer patients against fetal antigens: leukocyte migration studies.

Hypertonic extracts from human fetuses (10--22 wk of gestation) were used to test the sensitizaton of leukocytes from cancer patients against fetal antigens in a direct, microcapillary tube assay system. Leukocytes were simultaneously exposed to a panel of allogeneic tumor extracts and a panel of fetal extracts. Leukocytes from 24 gastric cancer patients, 43 colorectal cancer patients, and 13 lung cancer patients were assayed with extracts obtained from gastric, colorectal, and oat cell carcinomas, respectively, and these extracts were also used with leukocytes from 41 patients bearing tumors of various other organs. Significant migration inhibition by tumor extracts was observed in 81.6% of the tests with gastric cancer, 67.4% of the tests with colorectal cancer, 69.0% of the tests with lung cancer, and 51.2% of the tests with other types of cancer. With fetal extracts, significant migration inhibition occurred in 58.3, 58.7, 59.6, and 54.9% of the tests, respectively. Reactivity against fetal extracts did not depend on the gestation age of the fetuses used for extraction. The conclusion was reached that the leukocytes of most of the cancer patients were sensitized against substances contained in fetal extracts irrespective of the type of tumor of the leukocyte donor. The cross-reactivity pattern suggested that 3-M KCl extracts of whole human fetuses contained a complex mixture of specificities related to the various fetal organs and tissues, which may have represented counterparts to most of the tumor-associated specificities.

Antigens↗