University of Pennsylvania

Novartis Ag

The Scripps Research Institute

Southwest Research Institute

Wayne State University

The Trustees of the University of Pennyslvania

Engels, Boris

Milone, Michael C.

Wang, Enxiu

Michael C Milone

Carl H June

Bruce L Levine

David L Porter

Michael D Kalos

Jennifer Brogdon

David Jonathan Glass

Qilong Wu

Joan Mannick

Leon Murphy

Aimee S Payne

Christoph T Ellebrecht

Andreas Loew

Yongqiang Wang

Marco Ruella

Hilmar Erhard Ebersbach

Huijuan Song

Jiquan Zhang

Daniel J Powell

Saar Gill

Boris Engels

Reshma Singh

Yangbing Zhao

Jian Ling

Christoph Rader

Donald L Siegel

James L Riley

Brian Edward Vash

Jan Weiler

Brian Walter Granda

Lawrence G Lum

Li Zhou

Thomas Huber

Abhishek Garg

Carla Guimaraes

Andrei Alexandrovich Golosov

Vijay Bhoj

Jan J Melenhorst

Felipe Bedoya

Enxiu Wang

Celeste Richardson

Saad Kenderian

Saba Ghassemi

Zoe Zheng

Eugene Choi

Heather Huet

Gabriela Plesa

Lai Wei

Qiumei Yang

Julia Jascur

Gregory Beatty

Neeraja Idamakanti

William Raj Sellers

John Hastewell

Archana Thakur

Omkar U Kawalekar

Rachel Leibman

Kreg A Zimmern

Avery D Posey

Hans Bitter

Elena Orlando

Gregory Motz

Nathan Amar Singh

Sangwook Oh

David M Barrett

Corin Dorfmeier

Nicholas Wilcox

Jihyun Lee

David Maxwell Barrett

Abhishnek Garg

The invention provides methods of making immune effector cells (e.g., T cells, NK cells) that can be engineered to express a chimeric antigen receptor (CAR), compositions and reaction mixtures comprising the same, and methods of treatment using the same.

Methods for improving the efficacy and expansion of immune cells

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

Treatment of cancer using humanized anti-BCMA chimeric antigen receptor

Described herein is a beads-free bioprocessor as an automated and cost-effective T cell processing and manufacturing platform. T cells are a core component in CAR T cell therapies for cancer treatment, but are difficult to manufacture to scale in clinically relevant quantities. The 3D bioprocessor provides an alternative device that is scalable, beads-free, easy-to-use, and cost-effective for using CAR T cell therapy in cancer immunotherapy. Besides CAR T cell application, this platform technology has potential for many other applications such as cancer cell isolation.

Apparatus

The present invention relates to compositions and methods for treating of a HIV infected mammal using a CD4 membrane-bound chimeric receptor or a HIV specific scFvs CARs. One aspect includes a modified T cell and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with HIV infection.

Method of redirecting t cells to treat HIV infection

The present invention provides compositions and methods for regulating the specificity and activity of immune effector cells for use in immunotherapy. In one embodiment, the invention provides a type of chimeric antigen receptor (CAR) wherein the CAR is termed a 'NKR-CAR' which is a CAR design comprising a component of a receptor naturally found on natural killer (NK) cells. In one embodiment, the NK receptor includes but is not limited to a naturally occurring activating and inhibitory receptor of NK cells known as a killer cell immunoglobulin-like receptor (KIR).

Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy

The present invention relates to compositions and methods for treating diseases, disorders or conditions associated with the expression of the Glycosyl-phosphatidylinositol (GPI)-linked GDNF family α-receptor 4 (GFRα4).

Treatment of cancer using GFR alpha-4 chimeric antigen receptor

The present invention provides compositions and methods for regulating the specificity and activity of T cells. In one embodiment, the invention provides a type of chimeric antigen receptor (CAR) wherein the CAR is termed a 'KIR-CAR' which is a CAR design comprising a component of a receptor naturally found on natural killer (NK) cells. In one embodiment, the NK receptor includes but is not limited to a naturally occurring activating and inhibitory receptor of NK cells known as a killer cell immunoglobulin-like receptor (KIR).

The invention includes a chimeric autoantibody receptor (CAAR) specific for anti-muscle-specific kinase (MuSK) B cell receptor (BCR), compositions comprising the CAAR, polynucleotides encoding the CAAR, vectors comprising a polynucleotide encoding the CAAR, and recombinant cells comprising the CAAR.

Compositions and methods of muscle specific kinase chimeric autoantibody receptor cells

Methods for improving the efficacy and expansion of chimeric antigen receptor-expressing cells

The present invention relates to compositions and methods for enhancing T cell metabolism and activity for more effective adoptive T cell therapy. By expressing an chimeric antigen receptor and bispecific antibodies in T cells, the T cells are metabolically enhanced with improved cytotoxicity and resistance to immunosuppression imposed by tumor microenvironments. Certain aspects include modified T cells and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity.

Methods and compositions for cells expressing a chimeric intracellular signaling molecule

The present invention relates to compositions and methods for enhancing T cell metabolism and activity for more effective adoptive T cell therapy. By expressing an intracellular signaling molecule in T cells, the T cells are metabolically enhanced with improved cytotoxicity and resistance to immunosuppression imposed by tumor microenvironments. One aspect includes a modified T cell and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity.

The invention provides compositions and methods for treating diseases associated with expression of CD123. The invention also relates to chimeric antigen receptor (CAR) specific to CD123, vectors encoding the same, and recombinant cells comprising the CD123 CAR. The invention also includes methods of administering a genetically modified cell expressing a CAR that comprises a CD123 binding domain.

Treatment of cancer using a CD123 chimeric antigen receptor

The invention includes compositions comprising at least one chimeric autoantibody receptor (CAAR) specific for an autoantibody, vectors comprising the same, compositions comprising CAAR vectors packaged in viral particles, and recombinant T cells comprising the CAAR. The invention also includes methods of making a genetically modified T cell expressing a CAAR (CAART) wherein the expressed CAAR comprises a desmoglein extracellular domain.

Compositions and methods of chimeric autoantibody receptor T cells

Compositions and methods relating to regulatable chimeric antigen receptors (RCARs), where the intracellular signaling or proliferation of the RCAR can be controlled to optimize the use of an RCAR-expressing cell to provide an immune response, are provided. For example, a RCAR can comprise a dimerization switch that, upon the presence of a dimerization molecule, can couple an intracellular signaling domain to an extracellular recognition element, e.g., an antigen binding domain, an inhibitory counter ligand binding domain, or costimulatory ECD domain. An RCAR can be engineered to include an appropriate antigen binding domain that is specific to a desired antigen target and used in the treatment of a disease.

Regulatable chimeric antigen receptor

Method using a three-dimensional bioprocessor

Growing community of inventors

Cherry Hill, NJ, United States of America

Michael C Milone