The United States of America, as Represented by the Secretary, Department of Health and Human Services

Memorial Sloan Kettering Cancer Center

Purdue Research Foundation

The Children's Hospital of Philadelphia

Yang Feng

Dimiter Stanchev Dimitrov

Michel Sadelain

Philip Stewart Low

Prasad S Adusumilli

Jiayin Shen

Reuben Benjamin

Ira H Pastan

Zhongyu Zhu

Weizao Chen

John M Maris

Robyn Tovah Sussman

The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., multiple myeloma). It relates to anti-CD56 antibodies, chimeric antigen receptors (CARs) that specifically target human CD56, and immunoresponsive cells comprising such CARs. The presently disclosed CD56-specific CARs have enhanced immune-activating properties, including anti-tumor activity.

Methods of treatments using antigen-binding proteins targeting CD56

The presently disclosed subject matter provides for methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to chimeric antigen receptors (CARs) that specifically target human mesothelin, and immunoresponsive cells comprising such CARs. The presently disclosed mesothelin-targeted CARs have enhanced immune-activating properties, including anti-tumor activity.

Method of reducing mesothelin-expressing tumor burden by administration of T cells comprising mesothelin-targeted chimeric antigen receptors

Antigen-binding proteins targeting CD56 and uses thereof

Mesothelin-targeted chimeric antigen receptors and uses thereof

The identification and characterization of two fully human CD56-specific monoclonal antibodies targeting spatially separated epitopes proximal and distal to the plasma membrane is described. Also described are antibody-drug conjugates (ADCs) of the identified antibodies and their use for targeting CD56-expressing tumor cells.

Antibody-drug conjugates for targeting CD56-positive tumors

Mesothelin-targeted chimeric antigen receptors and methods of making them

Human anti-human folate receptor beta antibodies and antigen-binding fragments thereof are described, as well as methods of using such antibodies and fragments to treat inflammatory disorders or cancers expressing cell surface FR&#x3b2;.

Anti-human folate receptor beta antibodies and methods of use

Monoclonal antibodies (mAbs), antigen binding fragments and engineered antibody domains (eAds) that specifically bind IGF-II are disclosed herein. In some embodiments, these mAbs and eAds are included in a bispecific mAb. In some embodiments, the bispecific antibody specifically binds two different epitopes of IGF-II. Methods of using these mAbs, antigen binding fragments, and eAds, bispecific antibodies, and nucleic acids encoding these mAbs, antigen binding fragments, and eAds, bispecific antibodies are also disclosed.

Monospecific and bispecific human monoclonal antibodies targeting insulin-like growth factor II (IGF-II)

The present invention provides antibodies and antibody fragments that specifically recognize and agonize the death receptor 4 (DR4). Also provided in the invention are polynucleotides and vectors that encode such molecules and host cells that harbor the polynucleotides or vectors.

Anti-DR4 agonist antibodies

Human anti-human folate receptor beta (FR&#x3b2;) antibodies and antigen-binding fragments thereof are described, as well as methods of using such antibodies and fragments to treat inflammatory disorders or cancers expressing cell surface FR&#x3b2;.

Disclosed herein are isolated human monoclonal antibodies that specifically bind human mesothelin with a binding affinity of about 25 nM or less. 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 human mesothelin 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.

Human anti-mesothelin monoclonal antibodies

Disclosed herein are isolated monoclonal human antibodies that specifically binds insulin-like growth factor II (IGF-II) with an equilibrium dissociation constant (K) of 1 nM or less, wherein the antibody bind IGF-I with an equilibrium dissociation constant (K) of 1 mM or greater. The antibodies inhibit phosphorylation of the insulin-like growth factor receptor. Nucleic acids encoding these antibodies, expression vectors including these nucleic acids, and isolated host cells that express the nucleic acids are also disclosed. The antibodies can be used to detect human IGF-II in a sample. Methods of diagnosing a tumor are disclosed herein that utilize these antibodies. Methods of treating a subject with a tumor are also disclosed.

Growing community of inventors

Frederick, MD, United States of America

Yang Feng