Cetus Corporation

Chiron Corporation

The Medical College of Wisconsin, Inc.

Cetus Oncology Corporation

Jeffrey L Winkelhake

Robert Zimmerman

David B Ring

Walter J Laird

Arthur E Frankel

Michael J Bjorn

John D Young

Robert J Bauer

The present application relates to a method for enhancing the therapeutic index of a compound that is useful to treat tumors. More specifically, the present invention relates to a method for administering IL-2 to a tumor patient to maximize the therapeutic efficacy and minimize the toxicity.

Method for enhancing the anti-tumor therapeutic index of interleukin-2

Anti-tumor activity in mammals can be augmented by administering to the mammalian host a synergistically effective amount of TNF and IL-2 or of TNF and IFN-.beta., or of TNF, IL-2 and IFN-.beta. in combination. The composition of TNF and IL-2 and/or IFN-.beta. may be prepared in vitro or administered separately to the host. If the TNF and IL-2 are administered sequentially, the TNF must be administered prior to the IL-2 to obtain synergy. The composition is useful for treating such cancers as mastocytoma, melanoma, leukemia, lymphoma, mammary adenocarcinoma, and pharyngeal squamous cell carcinoma.

Combination therapy using interleukin-2 and tumor necrosis factor

Immunotoxins comprising a cytotoxic moiety and an antigen binding portion selected from the group consisting of Fab, Fab' and F(ab').sub.2 fragments of a monoclonal antibody, which binds to human ovarian cancer tissue, having one of the following capabilities are claimed: cytotoxic ID.sub.50 of about 10 nM or less against human ovarian cancer cells, retardation of human ovarian cancer tumor growth in mammals, or extension of survival of a mammal carrying a human ovarian cancer tumor. Antigens or epitopes to which the monoclonal antibodies bind are identified and characterize the immunotoxins. In a preferred embodiment an immunotoxin comprising at least an antigen binding portion of a monoclonal antibody, which binds to human transferrin receptor, but does not block binding of transferrin to the receptor, is described and claimed. Immunotoxin comprising the F(ab').sub.2 region of the antitransferrin monoclonal antibody are also claimed. Methods of killing human ovarian cancer cells, retarding the growth of human ovarian cancer tumors in mammals and extending the survial of mammals carrying human ovarian cancer tumors are claimed.

Anti-human ovarian cancer immunotoxins and methods of use thereof

Human myeloma fusing lines and human/human hybridomas produced therefrom are disclosed. In one embodiment, the myeloma cell line is HAT sensitive, does not secrete detectable levels of Epstein-Barr virus EBNA-I protein, and does not secrete or elaborate detectable levels of myeloma immunoglobulin. The myeloma cell line and resulting hybridoma are stable over time, and thus permit production of commercial quantities of human monoclonal antibody.

Myelomas for producing human/human hybridomas

Growing community of inventors

Emeryville, CA, United States of America

Jeffrey L Winkelhake