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R Herberman

Publications and source records attributed to R Herberman.

28 records · Page 2Linked to original sources
PubMed1972

Receptors for complement and immunoglobulin on human leukemic cells and human lymphoblastoid cell lines.

The bone marrow-derived (B) lymphocyte can be identified by the presence of easily detectable surface immunoglobulin and a receptor for antigen-antibody-complement complexes (EAC'). Monocytes and macrophages also bear a receptor for EAC' and in addition possess a receptor for red cell-IgG complexes (EA). Thymus-derived (T) lymphocytes bear neither of these receptors. The cells of 15 patients with leukemia and 19 human lymphoblastoid cell lines were examined for the presence of the EAC' and EA receptors. Of the human leukemias studied, only the cells from the patients with chronic lymphatic leukemia (CLL) possess the EAC' receptor. The EA receptor could not be demonstrated on CLL cells; hence, CLL cells bear the lymphocyte EAC' receptor and by this criteria represent B lymphocytes. 12/19 of the cell lines studied could be classified as B lymphocytes by the presence of the EAC' receptor and absence of the EA receptor. 2/19 cell lines possessed both the EAC' and EA receptors and thus resemble the monocyte. 5/19 cell lines had no detectable receptor for EAC' or EA. The approach presented in this study for the classification of leukemias and cell lines as to their B lymphocyte, T lymphocyte, or monocyte origin may have useful diagnostic and therapeutic implications.

Animals↗
PubMedDate not supplied

Immune response against 3LL Lewis lung carcinoma potentiates the therapeutic efficacy of endostatin.

The ability of the antitumor immune response to potentiate the therapeutic efficacy of the antiangiogenic agent endostatin was investigated. The antitumor effects of endostatin were tested against weakly immunogenic 3LL Lewis lung carcinoma and its highly immunogenic variant 3LL-C75. Using in vivo Matrigel assay, it was found that the recombinant endostatin produced in the authors' laboratory has a potent antiangiogenic effect. Endostatin manifested a more potent antitumor effect against highly immunogenic 3LL-C75 than weakly immunogenic 3LL tumor. Endostatin induced regression of immunogenic 3LL-C75 tumor in 40% of C57BL/6 mice, whereas partial inhibition and no regression were found in mice bearing weakly immunogenic 3LL tumor. 3LL and 3LL-C75 cells produced similar amounts of Vascular Endothelial Growth Factor, and immunohistochemical analysis revealed that endostatin treatment reduced microvessel density in both 3LL and 3LL-C75 tumors. However, infiltration of T lymphocytes was observed in 3LL-C75 but not in 3LL tumors. These results suggest that the host's immune response may potentiate the antitumor effects of antiangiogenic agents. This possibility was further supported by findings that the antitumor activity of endostatin against 3LL-C75 tumor was lower in immunodeficient than in immunocompetent mice. Stimulation of immune response against 3LL tumor by vaccination with highly immunogenic 3LL-C75 cells substantially increased the antitumor effect of endostatain, resulting in a complete and permanent regression of 3LL tumor in 50% of mice. Tumor vaccination or endostatin treatment applied separately inhibited but did not induce regression of 3LL tumor. These results suggest that the combined attack against tumor cells and the tumor vascular system using antitumor immune mechanisms and antiangiogenic drugs can be a promising strategy for cancer treatment.

Angiogenesis Inhibitors↗
PubMedDate not supplied

Evidence for indirect involvement of the H-2Kb gene in the regulation of natural killer sensitivity of BL6 melanoma cells.

We have previously demonstrated that transfection of BL6-8 melanoma cells with the H-2Kb gene increased their sensitivity to natural killer (NK)- and natural cytotoxic (NC) cell-mediated cytotoxicity, and resulted in alterations of various cell characteristics such as the loss of melanoma-associated antigen (MAA), and the appearance of Griffonia simplicifolia 1B4 (GS1B4)- and soybean agglutinin (SBA)-lectin-binding sites. In the present study the BL6-8 melanoma clone was transfected with the H-2Kb gene without cotransfection of the neomycin resistance (neor) gene, and transfected cells were isolated on the basis of their low sialylation and ability to bind to SBA-agarose beads. 38 out of 47 analyzed clones were morphologically distinguishable, expressed the H-2Kb gene, lost the MAA and gained SBA- and GS1B4-lectin-binding sites (H-2Kb+, MAA-, SBA+, GS1B4+), whereas only 5 clones were morphologically and phenotypically unchanged (H-2Kb-, MAA+, SBA-, GS1B4-). The remaining 4 clones were morphologically changed, lost MAA and gained SBA- and GS1B4-binding epitopes, but did not express H-2Kb antigen (H-2Kb-, MAA-, SBA+, GS1B4+). Analysis of the NK sensitivity of H-2Kb-gene-transfected clones revealed that H-2Kb+, MAA-, SBA+, GS1B4+ clones were highly sensitive to NK cell lysis, whereas H-2Kb-, MAA+, SBA-, GS1B4- clones were NK resistant. It is of particular note that the 4 clones that did not express H-2Kb antigen but had other phenotypic changes (H-2Kb-, MAA-, SBA+, GS1B4+) were also highly sensitive to NK cells. The NK sensitivity of H-2Kb-transfected cells was closely associated with their increased ability to compete with YAC-1 cells for effector cells in a cold-target inhibition assay. Thus, the data obtained indicate that H-2Kb molecules in BL6-8 melanoma cells are not required for interaction with the effector cells, and H-2Kb-induced alterations in membrane carbohydrates and/or expression of the retrovirus-associated MAA might be important for the increase NK sensitivity of BL6-8 melanoma cells.

DNA, Neoplasm↗