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

The United States of America As Represented by the Department of Health

University of Minnesota

Intima Bioscience, Inc.

Kite Pharma, Inc.

Other

The United States of America As Represented by the Secretary of

Yeda Research and Develpment & Co. Ltd

Immunocore Limited

Wilson Wolf Manufacturing Corporation

The Government of the United States of America, As Represented by the

Therion Biologics Corporation

The United States of America As Represented by the Secretary, Department

Istituto Superiore Di Sanita

The Government of the United States of America

Steven A Rosenberg

Paul F Robbins

Richard A Morgan

Nicholas P Restifo

Yutaka Kawakami

Christian S Hinrichs

Yong-Chen Lu

Beau R Webber

Branden Moriarity

Modassir Choudhry

Douglas C Palmer

Eric Tran

Maria R Parkhurst

Rong-Fu Wang

Patrick Hwu

Anna Pasetto

Zhili Zheng

James Noble Kochenderfer

Adrian I Bot

Alena Gros

Jeffrey S Wiezorek

William Go

Rajul Jain

Mark E Dudley

Gang Zeng

Rong Fu Wang

Steven A Feldman

Rami Yoseph

Zhiya Yu

David Largaespada

R Scott McIvor

Igor Bacik

W French Anderson

Ira H Pastan

John R Wilson

Drew M Pardoll

Li Liu

Suzanne L Topalian

Xin Yao

R Michael Blaese

Dennis L Panicali

Adam Shultz Adler

Linda R Gritz

Zelig Eshhar

Elizabeth A Jaffee

Robert L Somerville

Edward A Berger

Tova Waks

Richard Arthur Morgan

Nachimuthu Chinnasamy

Gal Cafri

Jonathan W Yewdell

Shannon Faith Rosati

Lydie Cassard

Dhanalakshmi Chinnasamy

Jack R Bennink

Drew C Deniger

Marianna Sabatino

Shiqui Zhu

Gideon Gross

Ke Liu

Sri Krishna

Rejean LaPointe

Mark Reeves

Timothy L Frankel

John R Wunderlich

Barna Dey

Ling Zhang

Arianne Perez

Bhavik Patel

Daniel Schindler

Cary Hsu

Michael H Kershaw

Hung Khong

Suzane L Topalian

Jianjian Jin

Michael Nishimura

Jack R Bennick

Parisa Malekzadeh

Winifred M Lo

Peter Fitzgerald

Jared J Gartner

Mustafa H Ghanem

David Stroncek

Peter Peng

Alan David Bennett

Gregoire Y Altan-Bonnet

Marc Better

The invention provides methods of increasing the efficacy of a T cell therapy in a patient in need thereof. The invention includes a method of conditioning a patient prior to a T cell therapy, wherein the conditioning involves administering a combination of cyclophosphamide and fludarabine.

Methods of conditioning patients for T cell therapy

Disclosed is an isolated or purified T cell receptor (TCR), wherein the TCR has antigenic specificity for a mutated human RAS amino acid sequence with a substitution of glycine at position 12 with arginine. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

HLA class II-restricted t cell receptors against RAS with G12R mutation

The invention provides an isolated or purified T cell receptor (TCR) having antigenic specificity for a) melanoma antigen family A (MAGE A)-3 in the context of HLA-A1 or b) MAGE-A12 in the context of HLA-Cw7. The invention further provides related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells. Further provided by the invention are antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the invention. Methods of detecting the presence of cancer in a host and methods of treating or preventing cancer in a host are further provided by the invention.

T cell receptors recognizing HLA-A1-restricted MAGE-A3

The invention provides an isolated or purified T-cell receptor (TCR) having antigenic specificity for MHC Class II-restricted MAGE-A3. The invention further provides related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells. Further provided by the invention are antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the invention. Methods of detecting the presence of cancer in a host and methods of treating or preventing cancer in a mammal are further provided by the invention.

T cell receptors recognizing MHC class II-restricted MAGE-A3

Disclosed is an isolated or purified T cell receptor (TCR) having antigenic specificity for mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) presented in the context of an HLA-Cw*0802 molecule. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

Anti-KRAS-G12D T cell receptors

Disclosed is an isolated or purified T cell receptor (TCR), wherein the TCR has antigenic specificity for mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) presented by a human leukocyte antigen (HLA) Class II molecule. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

HLA class II-restricted t cell receptors against mutated RAS

Disclosed are methods of selectively expanding a number of T cells. The methods may comprise: modifying human T cells to express a TCR, wherein the TCR comprises a murine constant region; producing a population of cells comprising a number of human T cells expressing the TCR and a number of human T cells not expressing the TCR; and culturing the population of cells in the presence of (i) irradiated feeder cells, (ii) one or more cytokines, and (iii) an antibody, or an antigen-binding portion thereof, wherein the antibody has antigenic specificity for the murine constant region of the TCR, so as to selectively expand the number of T cells expressing the TCR over the number of T cells not expressing the TCR. Also disclosed are related populations of cells, pharmaceutical compositions, and methods of treating or preventing cancer.

Methods for selectively expanding cells expressing a TCR with a murine constant region

Disclosed are methods of obtaining a cell population enriched for T cells having antigenic specificity for a cancer-specific mutation using in vitro stimulation of memory T cells. Also disclosed are related methods of isolating a T cell receptor (TCR), populations of cells, TCRs or antigen-binding portions thereof, pharmaceutical compositions, and methods of treating or preventing cancer.

Methods of enriching cell populations for cancer-specific T cells using in vitro stimulation of memory T cells

Disclosed is a T cell receptor (TCR) having antigenic specificity for an HLA-A2-restricted epitope of human papillomavirus (HPV) 16 E6, E6. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells are also provided. Antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the invention are also provided. Also disclosed are methods of detecting the presence of a condition in a mammal and methods of treating or preventing a condition in a mammal, wherein the condition is cancer, HPV 16 infection, or HPV-positive premalignancy.

Anti-human papillomavirus 16 E6 T cell receptors

Disclosed are methods of isolating T cells having antigenic specificity for a mutated amino acid sequence encoded by a cancer-specific mutation, the method comprising: identifying one or more genes in the nucleic acid of a cancer cell of a patient, each gene containing a cancer-specific mutation that encodes a mutated amino acid sequence; inducing autologous APCs of the patient to present the mutated amino acid sequence; co-culturing autologous T cells of the patient with the autologous APCs that present the mutated amino acid sequence; and selecting the autologous T cells. Also disclosed are related methods of preparing a population of cells, populations of cells, pharmaceutical compositions, and methods of treating or preventing cancer.

Methods of isolating T cells having antigenic specificity for a cancer-specific mutation

Disclosed are methods of preparing an isolated population of dendritic cells, isolated populations of dendritic cells prepared by the methods, and pharmaceutical compositions comprising the isolated population of dendritic cells. Also disclosed are methods of treating or preventing cancer using the isolated population of dendritic cells or pharmaceutical compositions.

Methods of preparing an isolated population of dendritic cells and methods of treating cancer using same

Disclosed is an isolated or purified T cell receptor (TCR) having antigenic specificity for mutated human p53. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

T cell receptors recognizing mutated P53

Genetically modified compositions, such as non-viral vectors and T cells, for treating cancer are disclosed. Also disclosed are the methods of making and using the genetically modified compositions in treating cancer.

Intracellular genomic transplant and methods of therapy

Disclosed are methods of preparing an isolated population of human papillomavirus (HPV)-specific T cells comprise dividing an HPV-positive tumor sample into multiple fragments; separately culturing the multiple fragments; obtaining T cells from the cultured multiple fragments; testing the T cells for specific autologous HPV-positive tumor recognition; selecting the T cells that exhibit specific autologous HPV-positive tumor recognition; and expanding the number of selected T cells to produce a population of HPV-specific T cells for adoptive cell therapy. Related methods of treating or preventing cancer using the T cells are also disclosed.

Methods of preparing anti-human papillomavirus antigen T cells

Growing community of inventors

Potomac, MD, United States of America

Steven A Rosenberg