The Salk Institute for Biological Studies

University of California

Ian S Trowbridge

Suhaila N White

Tony Hunter

Raymond Taetle

Clare M Isacke

M Bishr Omary

Combinations of monoclonal antibodies which are highly effective for inhibiting cell growth and methods for inhibiting cell growth employing novel combinations of monoclonal antibodies are disclosed. The antibodies employed are capable of binding to the human transferrin receptor glycoprotein and, in combination, usually exhibit a substantially greater inhibition of cell growth than either of the antibodies individually when administered in comparable amounts, e.g. at saturation conditions. In preferred combinations, at least one member of the combination is individually highly effective to inhibit cell growth and at least one other member of the combination is individually substantially ineffective to inhibit cell growth. Combinations are selected based upon an in vitro screening test using CCRF-CEM cells which express the human Tf receptor.

Enhanced inhibition of tumor cell proliferation using a combination of

Monoclonal antibodies have been produced which specifically bind to epitopes found in the cytoplasmic domain of the transferrin receptor (TR). The antibodies are useful for isolating sequences in a sample which contain TR cytoplasmic domain.

Monoclonal antibodies reactive with transferrin receptor cytoplasmic

The present invention provides monoclonal antibodies which are specific for one but not both of human lipocortin-I and human lipocortin-II, as well as cultures of hybridomas and other types of cells producing such antibodies.

Anti-lipocortin-I and anti-lipocortin-II monoclonal antibodies

Monoclonal antibodies are produced for a glycoprotein which is selectively expressed on the surface of human proliferating and immature hematopoietic cells but which is absent from normal peripheral blood cells. Mice are inoculated with human hematopoietic cells or fragments thereof, and spleen cells obtained from the mice are fused with mice myeloma cells to product hybridomas. The hybridomas are cultured as clones, and antibodies obtained from the individual clones are tested for their specificity for hematopoietic cells. Clones which produce antibodies specific for proliferating and immature hematopoietic cells are selected for further culturing to produce the antibody, and the antibody is obtained from the culture growth medium or from ascitic fluid of mice bearing the hybridoma tumor.

Hybridomas producing monoclonal antibodies specific for a human cell

Monoclonal antibodies are produced for a family of glycoproteins which are selectively expressed on the surface of nucleated human hematopoietic cells but which are absent from other normal human cells. Mice are inoculated with human hematopoietic cells or fragments thereof, and spleen cells obtained from the mice are fused with murine myeloma cells to produce hybridomas. The hybridomas are cultured as clones, and antibodies obtained from the individual clones are tested for their specificity for surface glycoproteins of nucleated human hematopoietic cells. Antibodies can be obtained from the culture growth medium or from ascitic fluid of mice bearing the hybridoma tumor and can be used to distinguish lymphomas from carcinomas.

Monoclonal antibodies specific for human hematopoietic cell surface

Monoclonal antibodies are produced specific for the cell surface transferrin receptor of human cells. Animals are inoculated with purified human transferrin receptor glycoprotein, human hematopoietic cells or fragments thereof, and spleen cells obtained from the animals are fused with myeloma cells to produce hybridomas. The hybridomas are cultured as clones, and antibodies obtained from the individual clones are tested for their specificty for human transferrin receptor. Clones which produce antibodies specific for the receptor and that interfere with or block transferrin binding are selected for further culturing to produce the antibody, and the antibody is obtained from the culture growth medium or from ascitic fluid of an animal bearing a tumor of the hybridoma. Monoclonal antibodies which block transferrin binding are useful in regulating cell growth and for other therapeutic uses.

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San Diego, CA, United States of America

Ian S Trowbridge