Memorial Sloan Kettering Cancer Center

University of Washington

Millennium Pharmaceuticals Limited

Sloan-Kettering Institute for Cancer Research

Memorial Hospital for Cancer and Allied Diseases

Jorge Mansilla-Soto

Michel Sadelain

Justin Gabriel Andre Francois Eyquem

Justin Eyquem

Anton Dobrin

Michel W J Sadelain

John A Stamatoyannopoulos

George Stamatoyannopoulos

Xingyue He

Isabelle Riviere

Xiuyan Wang

Mingdong Liu

Gary Shapiro

Jie Sun

Judith Feucht

Sascha P Haubner

Mohamad Hamieh

John Stamatoyannopoulos

The invention provides a T cell wherein one or more therapeutic transgenes is integrated at a within the genome of the cell such that expression of the transgene is under control of an endogenous promoter of the T cell. The invention additional provides methods of making and using such cells to treat a subject with T cell therapy. The invention also provides a T cell wherein a recombinant nucleic acid sequence encoding a chimeric antigen receptor (CAR) is integrated at a first site within the genome of the cell such that the CAR is expressed by the cell at the surface of the cell, and wherein integration of the nucleic acid encoding the CAR at the first site reduces or prevents expression of a functional T cell receptor (TCR) complex at the surface of the cell. The invention additional provides methods of making and using such cells to treat a subject with CAR therapy.

Transgenic T cell and chimeric antigen receptor T cell compositions and related methods

The presently disclosed subject matter provides for chimeric receptors that target ADGRE2 and chimeric receptors that target CLEC12A. The presently disclosed subject matter also provides for cells comprising the ADGRE2-targeted chimeric receptors, cells comprising the CLEC12A-targeted chimeric receptors, and cells comprising the ADGRE2-targeted chimeric receptors and the CLEC12A-targeted chimeric receptors. The presently disclosed subject matter further provides uses of such cells for treating tumors, e.g., AML.

Chimeric receptors targeting ADGRE2 and/or CLEC12A and uses thereof

The presently disclosed subject matter provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to novel designs of T cell receptors (TCRs) and engineered immunoresponsive cells comprising the same. The novel TCR binds to an antigen in an HLA-independent manner. In certain embodiments, the novel TCR provides enhanced sensitivity for a target gene having a low expression level.

Cells comprising non-HLA restricted T cell receptors

The presently disclosed subject matter provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to novel designs of chimeric antigen receptors (CARs) and engineered immunoresponsive cells comprising the same. The engineered immunoresponsive cells comprising the novel CARs are antigen-directed and have extended persistence without compromising function.

Enhanced chimeric antigen receptors and uses thereof

The presently disclosed subject matter provides for expression cassettes that allow for expression of a globin gene or a functional portion thereof, vectors comprising thereof, and cells transduced with such expression cassettes and vectors. The presently disclosed subject matter further provides methods for treating a hemoglobinopathy in a subject comprising administering an effective amount of such transduced cells to the subject.

Globin gene therapy for treating hemoglobinopathies

Growing community of inventors

Forest Hills, NY, United States of America

Jorge Mansilla-Soto