University of Pennsylvania

The General Hospital Corporation

Novartis Ag

University of Pittsburgh

The Children's Hospital of Philadelphia

Massachusetts Institute of Technology

Harvard College

The Brigham and Women's Hospital, Inc.

Promab Biotechnologies, Inc.

Forevertek Biotechnology Co., Ltd

Marcela V Maus

Carl H June

Jennifer Brogdon

James L Riley

Andreas Loew

John Scholler

Robert H Vonderheide

Anna Thomas

Hideho Okada

Laura Alexandra Johnson

Katherine A High

Mark Cobbold

Federico Mingozzi

Daniel J Hui

Bryan Choi

Irene Scarfo

Sangeeta N Bhatia

Saar Gill

David Jonathan Glass

Lijun Wu

Joan Mannick

Vita Golubovskaya

Leon Murphy

David L Porter

Benjamin L Ebert

John C Byrd

Marco Ruella

Anna Vulpetti

Mariusz Wasik

Natarajan Muthusamy

Amy Jo Johnson

Daniela Angst

Saad Kenderian

Jason A Dubovsky

William Raj Sellers

Quinlan Sievers

Anna Kaskel

Felipe Bedoya

Max Jan

Arnav Chhabra

Matthew Frigault

Joseph Fraietta

Joseph A Fraietta

François Gessier

The invention provides modified an isolated T lymphocytes having reduced or eliminated expression of the T Cell Receptor, due to reduced or eliminated expression of a CD3ζ, T Cell Receptor Alpha Chain, or T Cell Receptor Beta Chain gene relative to a T lymphocyte without modification, where the isolated T lymphocyte expresses a protein comprising US6, UL40 viral protein and signal peptide, and UL18.

Modified T cells and methods of their use

Immunotolerant engineered human tissue constructs are provided that are suitable for implantation into subjects. In some embodiments, the immunotolerance is controllable by an inducible system. Methods of making and using the immunotolerant engineered tissue constructs are provided.

Compositions and methods for immune tolerance

The invention provides methods and compositions for use in treating cancer, which advantageously may be achieved by targeting of the tumor microenvironment.

Chimeric antigen receptor T cells targeting the tumor microenvironment

Described herein are methods for producing and utilizing T cells comprising chimeric antigen receptors (CAR) comprising a portion of the extracellular domain of a Tumor Necrosis Factor (TNF) superfamily receptor ligand, e.g., A PRoliferation-Inducing Ligand (APRIL). The CAR T cells of this present invention overcome resistance to anti-BCMA targeted therapies and utilize dimerizing and trimerizing transmembrane domains for optimal function. Further, this invention is related to methods of treating cancer, plasma cell diseases or disorders, or autoimmune diseases or disorders.

T cells expressing a chimeric antigen receptor

The present disclosure relates to therapeutic methods and clinically useful molecular switches, for which activity or degradation of a switch-presenting polypeptide can be precisely induced via administration or withdrawal of an FDA-approved drug. Certain aspects of the disclosure relate to an engineered drug-inducible heterodimeric system including a first polypeptide presenting a CRBN polypeptide disrupted for or lacking a DDB 1-interacting domain and a second polypeptide presenting a CRBN polypeptide substrate, where binding between the CRBN polypeptide and the CRBN polypeptide substrate are inducible via administration of an CFDA-approved thalidomide analog immunomodulatory drug (IMiD). Another aspect of the disclosure relates to a chimeric antigen receptor (CAR) that presents a minimal fragment of the CRBN polypeptide substrate IKZF3 capable of triggering proteasomal degradation of CAR upon administration of an FDA-approved IMiD.

Molecular switch-mediated control of engineered cells

The invention provides compositions and methods for treating diseases associated with expression of EGFRvIII. The invention also relates to chimeric antigen receptor (CAR) specific to EGFRvIII, vectors encoding the same, and recombinant T cells comprising the anti-EGFRvIII CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an anti-EGFRvIII binding domain.

Treatment of cancer using humanized anti-EGFRvIII chimeric antigen receptor

Described herein are methods for producing and utilizing an artificial antigen presenting cell (aAPC). An aAPC is engineered to express a first and second chimeric stimulatory receptor that specifically bind antigen presenting on a T cell of interest. The aAPC as described herein is designed for use in activating and/or expanding a T cell or chimeric antigen receptor (CAR) T cell. Further, this invention relates to methods of treating cancer by administering to a subject in need thereof an aAPC-activated CART cell.

Methods and compositions relating to ex vivo culture and modulation of T cells

Described herein are methods for producing and utilizing an alternative signal 1 domain to construct an optimally signaling CAR. Alternative signal 1 domains of the present technology are based on alternatives to CD3&#x3b6;, including mutated ITAMs from CD3&#x3b6; (which contains 3 IT AM motifs), truncations of CD3&#x3b6;, and alternative splice variants known as CD3s, CD3 theta, and artificial constructs engineered to express fusions between CD3s or CD30 and CD3&#x3b6;. CAR polypeptides comprising alternative signal 1 domains are utilized to engineer CAR T cells. Further, this technology related to methods of treating cancer by administering to a subject in need thereof CAR T cells comprising alternative signal 1 domains.

Chimeric antigen receptors based on alternative signal 1 domains

Compositions and methods are provided for inhibiting T cell mediated destruction of virally transduced, trangene containing cells.

Compositions and methods for detection and modulation of T cell mediated immune responses against viral vectors utilized for gene therapy

Described herein are chimeric antigen receptors (CARs) targeting CD37, as well as related molecules and methods.

Chimeric antigen receptors targeting CD37

The present invention is directed to a chimeric antigen receptor (CAR) fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) comprising Vand V, wherein scFv binds to a tumor antigen, (ii) a transmembrane domain, (iii) a co-stimulatory domain of GITR intracellular domain, and (iv) an activating domain. In one embodiment, the tumor antigen is human epidermal growth factor receptor (EGFR), human mesothelin, or human CD19. CARs having GITR intracellular domain as a co-stimulatory domain have certain advantages over other traditional CAR co-stimulatory domains.

Chimeric antigen receptors having GITR intracellular domain as co-stimulatory domain

The invention provides compositions and methods for treating diseases associated with expression of CD19. The invention also relates to chimeric antigen receptor (CAR) specific to CD19, vectors encoding the same, and recombinant T cells comprising the CD19 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD19 binding domain.

Treatment of cancer using humanized anti-CD19 chimeric antigen receptor

The invention provides compositions and methods for treating diseases associated with expression of CD19, e.g., by administering a recombinant T cell comprising the CD19 CAR as described herein, in combination with a kinase inhibitor, e.g., a kinase inhibitor described herein. The invention also provides kits and compositions described herein.

Treatment of cancer using anti-CD19 Chimeric Antigen Receptor

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Lexington, MA, United States of America

Marcela V Maus