University of California

Thomas James Kipps

Bing Cui

George F Widhopf, Ii

Mark J Cantwell

Charles E Prussak

Liguang Chen

Jian Yu

Andrew C Kummel

Bradley T Messmer

Ana B Sanchez

Manuel Ruidiaz

Sanjai Sharma

Paul A Insel

Lingzhi Zhang

Suping Zhang

Laura Rassenti

Joan R Kanter

Jianqianq Yu

Fiona Murray

Januario E Castro

Tetsuya Fukuda

Emanuela M Ghia

Charles Prussak

Yunqi Wu

Jianqiang Yu

Fionna Murray

Carlos E Prada

H Elizabeth Broome

Tomoyuki Endo

George F Widhopf

George Widhopf

George F Widhopf Ii

Provided herein are, inter alia, methods of identifying agents that are capable of inhibiting the binding (e.g., coupling) between a ROR1 protein and a ROR2 protein. By interfering with ROR1-ROR2 coupling (binding) the agents identified using the methods provided herein inhibit non-canonical Wnt5a signaling. Thus, the agents identified by the methods provided herein may, inter alia, be useful for cancer diagnosis and therapy.

Modulators of ROR1-ROR2 binding

Therapeutic antibodies having binding specificity for ROR-1 expressed on cancer cells (particularly leukemic and lymphomic cells) and pharmaceutical compositions containing one or more such antibodies for use in treating cancer. Methods for diagnosing such cancers through in vitro detection of binding to ROR-1 protein expressed on putative cancer cells are also provided.

Therapeutic antibodies against ROR-1 protein and methods for use of same

The present invention relates to pharmaceutical compositions and a method of inhibiting metastasis using anti-ROR1 antibodies or antigen binding fragments, ROR1 binding peptides and ROR1 vaccines.

Antibodies and vaccines for use in treating ROR1 cancers and inhibiting metastasis

There are provided, inter alia, compositions and methods for treatment of chemoresistant cancer (breast cancer). The methods include administering to a subject in need a therapeutically effective amount of a chemotherapeutic agent and a ROR-1 antagonist. Further provided are pharmaceutical compositions including chemotherapeutic agent, ROR-1 antagonist and a pharmaceutically acceptable excipient. In embodiments, the chemotherapeutic agent is paclitaxel and the ROR-1 antagonist is cirmtuzumab.

Combination treatment of chemoresistant cancers

There are provided, inter alia, compositions and methods for treatment of cancer. The methods include administering to a subject in need a therapeutically effective amount of a Bruton's tyrosine kinase (BTK) antagonist and a ROR-1 antagonist. Further provided are pharmaceutical compositions including a BTK antagonist, ROR-1 antagonist and a pharmaceutically acceptable excipient. In embodiments, the BTK antagonist is ibrutinib and the ROR-1 antagonist is cirmtuzumab.

Cancer treatment combinations

Compositions including an antibody single-chain variable fragment (scFv) conjugate that specifically binds to ROR1 tumor-associated antigen are provided. The anti-ROR1 scFv antibody and conjugates may include a biologically-active molecule. Such conjugates may comprise a chimeric receptor to direct T cells to respond to ROR1 cancer cells, Methods to use the scFV conjugates to target cells expressing ROR1 for therapeutic and diagnostic purposes are also provided.

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) single chain Fv antibody fragment conjugates and methods of use thereof

Complexes comprising a therapeutic monoclonal antibody and a peptide are provided. In some embodiments, the complexes may comprise a therapeutic monoclonal antibody which is not complexed to an epitope of a target protein and a peptide complexed to the therapeutic monoclonal antibody. In some embodiments, the peptide may have a length of about 5-40 amino acids and may comprise a mimetope recognized by the therapeutic monoclonal antibody, wherein the mimetope comprises a linear sequence of amino acids which is different than a linear sequence of amino acids in the epitope of the target protein.

Methods for detecting antibodies

Provided herein are, inter alia, methods of identifying agents that are capable inhibiting the binding (e.g., coupling) between a ROR1 protein and a ROR2 protein. By interfering with ROR1-ROR2 coupling (binding) the agents identified using the methods provided herein inhibit non-canonical Wnt5a signaling. Thus, the agents identified by the methods provided herein may, inter alia, be useful for cancer diagnosis and therapy.

Growing community of inventors

San Diego, CA, United States of America

Thomas James Kipps