University of Pittsburgh

The General Hospital Corporation

Health Research, Inc.

The University of North Carolina at Chapel Hill

University of Pennsylvania

The University of Texas System

Baylor College of Medicine

Memorial Sloan Kettering Cancer Center

Sloan-Kettering Institute for Cancer Research

Universitá Degli Studi Di Torino

Hauptman-Woodward Medical Research Institute, Inc.

Soldano Ferrone

Xinhui Wang

Elvira Favoino

Thomas P Conrads

Gianpietro Dotti

Brian L Hood

Wei Luo

Cristina Ferrone

Yangyang Wang

Nai-Kong V Cheung

Yvonne Paterson

Paulo Cesar Maciag

Ling Yu

Hongwei Du

Chun-Yen Tsao

Matthew Seavey

Federica Cavallo

Constantin G Ioannides

Elena Quaglino

Chien-Chung Chang

Debashis Ghosh

James L Murray

Hannah Reid Hudson

Federica Riccardo

Paulo MaCiag

Maddalena Arigoni

Francesco Sabbatino

Steven Isakoff

Joe Schwab

Raffaele Adolfo Calogero

Elena Dukhovlinova

Ming Cheng

Kouichiro Kawano

Paolo Buracco

Jeff Chi-Feng Hsu

Paulo Maciag

The present invention provides a chimeric antigen receptor (CAR) that recognizes CSPG4 as well as methods of use in the treatment of diseases and disorders.

Methods and compositions for chimeric antigen receptor targeting cancer cells

Embodiments of the disclosure include methods and compositions related to chimeric antigen receptors (CAR) that target chondroitin sulfate proteoglycan-4 (CSPG4). T cells transduced with a CSPG4-specific CAR are effective for inhibition of particular cancer cells that express CSPG4. In certain embodiments, the cancer is melanoma, breast cancer, head and neck cancer, mesothelioma, glioblastoma, or renal cancer.

CSGP4&#x2014;specific chimeric antigen receptor for cancer

Described herein are antibodies that bind chondroitin sulfate proteoglycan 4 (CSPG4) and, in particular, chimeric and humanized anti-CSPG4 antibodies and fragments thereof. Also provided herein are methods of using individual humanized antibodies or compositions thereof for the detection, prevention, and/or therapeutic treatment of CSPG4-related diseases, in particular, melanoma.

Anti-chondroitin sulfate proteoglycan 4 antibodies and uses thereof

Isolated monoclonal antibodies are disclosed herein that specifically bind endoplasmin. In some embodiments these antibodies are fully human. Recombinant nucleic acids encoding these antibodies, expression vectors including these nucleic acids, and host cells transformed with these expression vectors are also disclosed herein. In several embodiments the disclosed antibodies are of use for detecting and/or treating tumors that express endoplasmin, such as melanoma, breast cancer, head and neck squamous cell carcinoma, renal cancer, lung cancer, glioma, bladder cancer, ovarian cancer or pancreatic cancer. In one example, the tumor is a melanoma.

Antibodies to endoplasmin and their use

Embodiments of the present invention provide antibodies, antigen binding portions thereof, and other polypeptides (e.g., CARs), that specifically bind to CSPG4, an antigen expressed on cancer cells. Monoclonal antibodies, antibody-drug conjugates, and/or CAR-T-cells that specifically bind to CSPG4 positive cancer cells are also provided.

Anti-CSPG4 reagents and methods of treating cancer

A nucleic acid molecule encoding a chimeric chondroitin sulfate proteoglycan 4 (CSPG4) protein, wherein the chimeric CSPG4 protein comprises, from the N-terminal to the C-terminal: i) a first portion derived from the human CSPG4 sequence and a second portion derived from the canine CSPG4 sequence or ii) a first portion derived from the canine CSPG4 sequence and a second portion derived from the human CSPG4 sequence.

Nucleic acid molecules encoding for chimeric CSPG4 proteins and therapeutic uses thereof

The present invention provides a chimeric antigen receptor (CAR) that recognizes B7-H3 (CD276), as well as methods of use in the treatment of diseases and disorders.

Methods for treating cancer using a combination of an inhibitor of the sonic hedgehog signaling pathway (e.g., LDE225) with radiation and a tumor antigen-specific monoclonal antibody (e.g., heat shock protein (HSP) glucose regulated protein of 94000 daltons (Grp94)-specific mAb W9, or chondroitin sulfate proteoglycan 4 (CSPG4)-targeted mAbs), or with a BRAF inhibitor, e.g., in BRAF inhibitor resistant cancers.

Combination treatments with sonic hedgehog inhibitors

It is disclosed herein that condroitin sulfate proteoglycan 4 (CSPG4), also known as high molecular weight melanoma associated antigen, is overexpressed on basal breast carcinoma cells (BBC), specifically triple negative basal breast carcinoma cells (TNBC). Methods for detecting basal breast cancer in a subject are disclosed. Methods are also disclosed for inhibiting the growth of a basal breast cancer cell. These methods include contacting the basal breast cancer cell with an effective amount of an antibody that specifically binds CSPG4. Additional treatment methods, and the use of antibody panels, are also described herein.

Monoclonal antibodies for CSPG4 for the diagnosis and treatment of basal breast carcinoma

Disclosed herein are isolated human monoclonal antibodies, and functional fragments thereof, that specifically bind HMW-MAA. Nucleic acids encoding these antibodies, expression vectors including these nucleic acid molecules, and isolated host cells that express the nucleic acid molecules are also disclosed. The antibodies can be used to detect HMW-MAA in a sample. Methods of diagnosing cancer, or confirming a diagnosis of cancer, are disclosed herein that utilize these antibodies. Methods of treating a subject with cancer are also disclosed.

Fully human antibodies to high molecular weight-melanoma associated antigen and uses thereof

Combinations of agents that have a synergistic effect for the treatment of a tumor are disclosed herein. These combinations of agents can be used to treat tumors, wherein the cells of the cancer express a mutated BRAF. Methods are disclosed for treating a subject diagnosed with a tumor that expresses a mutated BRAF. The methods include administering to the subject (1) a therapeutically effective amount of an antibody or antigen binding fragment thereof that specifically binds high molecular weight melanoma associated antigen (HMW-MAA), also known as CSPG4; and (2) a therapeutically effective amount of a BRAF inhibitor. In some embodiments, the tumor is melanoma. In some embodiments the method includes selecting a subject with primary or secondary resistance to a BRAF inhibitor. In further embodiments, treating the tumor comprises decreasing the metastasis of the tumor. In additional embodiments, the BRAF inhibitor comprises PLX4032 or PLX4720.

Methods for treating a tumor using an antibody that specifically binds HMW-MAA

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Boston, MA, United States of America

Soldano Ferrone