University of California

The Salk Institute for Biological Studies

Raymond Taetle

Michael J Kelner

Trevor C McMorris

Ian S Trowbridge

Suhaila N White

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

Antineoplastic illudin analogs are provided of the formula: wherein R.sub.4, R.sub.5 and R.sub.6 are (C.sub.1 -C.sub.4)alkyl, Y is H, (C.sub.1 -C.sub.3)alkyl, (R.sub.4)R.sub.5)(R.sub.6)Si or alkanoyl ((C.sub.1 -C.sub.4)alkylC(O)) and R is CH.sub.2 OH, halo, benzyl optionally substituted with OY, or alkanoylmethyl (CH.sub.2 OC(O)R.sub.7), wherein R.sub.7 is (C.sub.1 -C.sub.4)alkyl, (C.sub.6 -C.sub.2)aryl or N(X).sub.2, wherein each X is H or (C.sub.1 -C.sub.4)alkyl, and the pharmaceutically-acceptable salts thereof.

Illudin analogs useful as antitumor agents

A compound to inhibit tumor cell growth in a subject in need of said therapy is provided, wherein said compound has the structure: ##STR1## wherein R is selected from the group consisting of: ##STR2## Tumor cells sensitive to inhibition by said compound are selected from the group consisting of a myeloid leukemia cell, a T-cell leukemia cell, a lung carcinoma cell, an ovarian carcinoma cell, and a breast carcinoma cell.

Illudin analogs

A therapeutic method is provided to inhibit tumor cell growth in a subject in need of said therapy is provided, comprising parenterally administering a therapeutic amount of a compound in a pharmaceutically acceptable carrier, wherein said compound has the structure: ##STR1## wherein R is selected from the group consisting of: ##STR2## and wherein said tumor cell is sensitive to inhibition by said compound and is selected from the group consisting of a myeloid leukemia cell, a T-cell leukemia cell, a lung carcinoma cell, an ovarian carcinoma cell, and a breast carcinoma cell.

Method of treating certain tumors using illudin analogs

A method of inhibiting certain tumor cell growth in a subject is provided comprising contacting the tumor with a therapeutic amount of an illudin S or illudin M analog having the structure ##STR1## wherein the analog is capable of inhibiting tumor cell growth without excessive toxicity to the subject and wherein

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Tucson, AZ, United States of America

Raymond Taetle