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

Leland Stanford Junior University

Biomed Valley Discoveries, Inc.

Crystal L Mackall

Rimas J Orentas

Dimiter Stanchev Dimitrov

Ira H Pastan

Evan Weber

Zhongyu Zhu

Saurabh Saha

Bradley St Croix

Robbie Majzner

Rachel Lynn

Jay A Berzofsky

Terry J Fry

Haiying Qin

Lee J Helman

Leon T Van Den Broeke

Elena Sotillo

Garry P Nolan

Ravindra Majeti

Jie Liu

Sean Bendall

Michael Z Lin

Michelle Monje-Deisseroth

Christopher Mount

Wan-Jen Hong

Waleed Haso

Yongzhi Karen Cui

Louai Labanieh

Zinaida Good

Rebecca Richards

Tom J Wandless

The present invention relates to T cell compositions and methods of using the same in the context of therapy and treatment. In particular, the invention provides T cells that are modified (e.g., genetically and/or functionally) to maintain functionality under conditions in which unmodified T cells display exhaustion. Compositions and methods disclosed herein find use in preventing exhaustion of engineered (e.g., chimeric antigen receptor (CAR) T cells) as well as non-engineered T cells thereby enhancing T cell function (e.g., activity against cancer or infectious disease).

Compositions and methods for inhibiting T cell exhaustion

Provided herein are cell surface receptors that include an extracellular binding domain, a transmembrane domain, an intracellular signaling domain, and a protease cleavage site disposed between the extracellular binding domain and the intracellular signaling domain. In certain aspects, the cell surface receptors are engineered cell surface receptors, such as chimeric antigen receptors (CARs). Also provided are cells that include such receptors (e.g., where the cells express the receptors on their surface) and pharmaceutical compositions including such cells. Nucleic acids that encode the cell surface receptors, cells including such nucleic acids, and pharmaceutical compositions including such cells, are also provided. Also provided are methods for regulating signaling of a cell surface receptor, and methods of using the cells of the present disclosure, including methods of using such cells to administer a regulatable cell-based therapy to an individual.

Regulatable cell surface receptors and related compositions and methods

Antigen binding domain polypeptides (ABD) specific for human CD93 are provided, which ABD may be formatted as antibodies, as chimeric antigen receptors, and the like. T cells comprising an anti-CD93 CAR are useful in the treatment of cancer, e.g. hematologic malignancies.

Therapeutic antigen binding proteins specific for CD93 and methods of use thereof

The present disclosure generally relates to compositions and methods useful for an adoptive cell therapy. Some embodiments of the disclosure relates to methods for producing a population of lymphocytes enriched in T stem cell memory cells (Tcells). Further provided are compositions containing a substantially pure population of Tcells that are therapeutically effective in treating various cancers, and kits containing such compositions. Methods for treating a subject having or suspected of having a cancer using the compositions and kits as disclosed herein are also provided.

Compositions and methods of expansion of T cell populations

An embodiment of the invention provides bicistronic chimeric antigen receptor (CAR) amino acid constructs. Nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CAR constructs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed. Methods of making the CAR constructs are disclosed.

Bicistronic chimeric antigen receptors and their uses

The present invention relates to T cell compositions and methods of using the same in the context of therapy and treatment. In particular, the invention provides chimeric antigen receptor (CAR) T cells that are modified to maintain functionality under conditions in which unmodified CAR T cells display exhaustion. Compositions and methods disclosed herein find use in inhibiting or reversing CAR T cell exhaustion (e.g., by modulating CAR surface expression) thereby enhancing CAR T cell function. Compositions and methods of the invention fmd use in both clinical and research settings, for example, within the fields of biology, immunology, medicine, and oncology.

Methods of treating T cell exhaustion by inhibiting or modulating T cell receptor signaling

The invention provides a chimeric antigen receptor (CAR) comprising an antigen binding domain comprising SEQ ID NOs: 1-6, a transmembrane domain, and an intracellular T cell signaling domain. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

M971 chimeric antigen receptors

Polypeptides and proteins that specifically bind to and immunologically recognize CD276 are disclosed. Chimeric antigen receptors (CARs), anti-CD276 binding moieties, nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the polypeptides and proteins are also disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

Anti-CD276 polypeptides, proteins, and chimeric antigen receptors

The invention relates to immunotherapeutic treatment of cancer. In particular, the invention relates to methods of treating cancer carrying a histone H3K27M (H3K27M) mutation (e.g., diffuse midline glioma with H3K27M mutation) using immunotherapeutic compositions comprising immune cells engineered to express GD2-specific chimeric antigen receptors.

Compositions and methods for treatment of cancers harboring an H3K27M mutation

The invention provides dual specific chimeric antigen receptors (CARs) having antigenic specificity for CD19 and CD22. Nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

Dual specific anti-CD22-anti-CD19 chimeric antigen receptors

Chimeric antigen receptors (CARs) that specifically bind to and immunologically recognize CD276 are disclosed. Related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the polypeptides and proteins are also disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

Anti-CD276 chimeric antigen receptors

Growing community of inventors

Bethesda, MD, United States of America

Crystal L Mackall