University of Pennsylvania

Novartis Ag

USA As Represented by Secretary of the Navy

University of Michigan

Genetics Institute, Inc.

Other

University of Pittsburgh

The Wistar Institute

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

University of Minnesota

Wayne State University

The Children's Hospital of Philadelphia

Dana-farber-cancer Institute Inc.

Craig B. Thompson

Jeffrey A. Ledbetter

Carl H June

Bruce L Levine

Michael C Milone

Yangbing Zhao

John Scholler

James L Riley

Michael D Kalos

Saar Gill

Jennifer Brogdon

Andreas Loew

Craig B Thompson

David L Porter

Marcela V Maus

Xiaojun Liu

Gary J Nabel

Daniel J Powell

Gary S Gray

Paul David Rennert

Marco Ruella

Michael Klichinsky

Avery D Posey

Robert H Vonderheide

Qilong Wu

David Jonathan Glass

Bruce Robert Blazar

Joan Mannick

Leon Murphy

Wayne R Godfrey

Huijuan Song

Richard G Carroll

Yongqiang Wang

Boris Engels

Hilmar Erhard Ebersbach

Jan J Melenhorst

Anne Chew

Felipe Bedoya

Gregory Beatty

Neeraja Idamakanti

Nicole Aqui

Stephen J Schuster

Anna Thomas

Matthew J Frigault

Saba Ghassemi

Zoe Zheng

Ming Lei

Reshma Singh

Lu Huang

Hideho Okada

Jennifer Bordeaux

Steven M Albelda

Li Zhou

Jimin Zhang

Na Li

Jiangtao Ren

Celeste Richardson

Thai Tran

Ellen Puré

Naveen Kumar Dakappagari

Ju Young Kim

Liang-Chuan Wang

Elena Orlando

Sonia Guedan Carrio

Laura Alexandra Johnson

Hans Bitter

Eugene Choi

Heather Huet

Patricia Taylor

Gabriela Plesa

Suil Kim

Chrystal Paulos

Steven Highfill

Devon Shedlock

Barbara Brannetti

Lawrence G Lum

Daniel H Fowler

Enxiu Wang

Keli Hippen

Archana Thakur

Megan M Davis

Megan M Suhoski

Gordon James Freeman

Jeffrey A Ledbetter

Thomas Huber

John C Byrd

Anna Vulpetti

Mariusz Wasik

Jiquan Zhang

Lai Wei

Amy Jo Johnson

Daniela Angst

Stephan Grupp

Ronald E Gress

Natarajan Muthusamy

Jason A Dubovsky

Qiumei Yang

Julia Jascur

Saad Kenderian

William Raj Sellers

The present invention relates generally to a fusion protein that when displayed on a cell can convert a negative signal into a positive signal in the cell. The fusion protein is a chimeric protein in that the protein comprises at least two domains, wherein the first domain is a polypeptide that is associated with a negative signal and the second domain is a polypeptide that is associated with a positive signal. Thus, the invention encompasses switch receptors that are able to switch negative signals to positive signals for enhancement of an immune response.

Switch costimulatory receptors

The present invention provides compositions and methods for generating a genetically modified T cells comprising a chimeric antigen receptor (CAR) having an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the T cell exhibits prolonged exponential expansion in culture that is ligand independent and independent of the addition of exogenous cytokines or feeder cells.

Compositions and methods for generating a persisting population of T cells useful for the treatment of cancer

The present invention relates to compositions and methods for generating a modified T cell with a nucleic acid capable of downregulating endogenous gene expression selected from the group consisting of TCR α chain, TCR β chain, beta-2 microglobulin, a HLA molecule, CTLA-4, PD1, and FAS and further comprising a nucleic acid encoding a modified T cell receptor (TCR) comprising affinity for a surface antigen on a target cell or an electroporated nucleic acid encoding a chimeric antigen receptor (CAR). Also included are methods and pharmaceutical compositions comprising the modified T cell for adoptive therapy and treating a condition, such as an autoimmune disease.

Altering gene expression in cart cells and uses thereof

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 one or more B-cell inhibitors, e.g., inhibitors of one or more of CD10, CD20, CD22, CD34, CD123, FLT-3, ROR1, CD79b, CD179b, or CD79a. The disclosure additionally features novel antigen binding domains and CAR molecules directed to CD20 and CD22, and uses, e.g., as monotherapies or in combination therapies. The invention also provides kits and compositions described herein.

CD20 therapies, CD22 therapies, and combination therapies with a CD19 chimeric antigen receptor (CAR)-expressing cell

The present invention provides compositions and methods for inducing a CAR mediated trans-signal in a T cell. The trans-signaling CAR T cells comprise a first CAR having a first signaling module and a second CAR having a distinct second signaling module. The present invention also provides cells comprising a plurality of types of CARs, wherein the plurality of types of CARs participate in trans-signaling to induce T cell activation.

Use of trans-signaling approach in chimeric antigen receptors

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 present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell expressing a CAR having an antigen binding domain, a transmembrane domain, a CD2 signaling domain, and a CD3 zeta signaling domain. The invention also includes incorporating CD2 into the CAR to alter the cytokine production of CAR-T cells in both negative and positive directions.

Use of the CD2 signaling domain in second-generation chimeric antigen receptors

The present invention includes compositions and methods for treating T cell lymphomas and leukemias. In certain aspects, the compositions and methods include CAR T cells targeting CD2, CD5, or CD7 and modified cells wherein CD2, CD5, or CD7 has been knocked-out.

Use of CD2/5/7 knock-out anti-CD2/5/7 chimeric antigen receptor T cells against T cell lymphomas and leukemias

The present invention includes compositions and methods for modifying a T cell with a nucleic acid encoding a switch molecule comprising an extracellular domain comprising a membrane receptor or fragment thereof and an intracellular domain comprising a signaling receptor or fragment thereof. In one aspect, a method comprises introducing a nucleic acid encoding a switch molecule and a nucleic acid encoding a soluble fusion protein and/or a nucleic acid encoding a bispecific antibody into a population of cells comprising T cells, wherein the T cells transiently expresses the switch molecule and soluble fusion protein or bispecific antibody. In other aspect, compositions of T cells and methods of treating a disease or condition, such as cancer or an autoimmune disease, are also included.

Compositions and methods for T cell delivery of therapeutic molecules

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

The invention provides T cells comprising nucleic acid sequence encoding a chimeric antigen receptor and a nucleic acid sequence encoding an enhancer of T cell priming, compositions including the T cells, and methods of using the T cells to treat diseases associated with the expression of disease-associated antigens.

Enhanced antigen presenting ability of RNA car T cells by co-introduction of costimulatory molecules

Provided are compositions and methods for treating diseases associated with expression of mesothelin. Also provided are a chimeric antigen receptor (CAR) specific to mesothelin, vectors encoding the same, and recombinant T cells comprising the mesothelin CAR. Further provided are methods of administering a genetically modified T cell expressing a CAR that comprises a mesothelin binding domain.

Human mesothelin chimeric antigen receptors and uses thereof

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 provides compositions and methods for treating cancer in a human. The invention includes administering a genetically modified Th17 cell to express a CAR having an antigen binding domain, a transmembrane domain, and an ICOS intracellular signaling domain.

Use of ICOS-based cars to enhance antitumor activity and car persistence

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

Growing community of inventors

Merion Station, PA, United States of America

Carl H June