Memorial Sloan Kettering Cancer Center

Ludwig Institute for Cancer Research Limited

Agenus Inc.

Health Research, Inc.

Takemasa Tsuji

Gerd J Ritter

Taha Merghoub

Marc A Van Dijk

David Schaer

Volker Seibert

Olivier Léger

Nicholas Stuart Wilson

Dennis John Underwood

Junko Matsuzaki

Kunle Odunsi

Jedd David Wolchok

Roberta Zappasodi

Ana M Gonzalez

Ekaterina Vladimirovna Breous-Nystrom

Jeremy Dale Waight

Daniel Hirschhorn-Cymerman

Adekunle Odunsi

Richard Koya

Marc Van Dijk

Volker Siebert

Olivier Leger

Nicolas S Wilson

Provided are compositions and methods for prophylaxis and/or therapy of a variety of cancers which express a NY-ESO-1 antigen. Included are recombinant T cell receptors (TCRs), polynucleotides encoding them, expression vectors that include the polynucleotides, and cells into which the polynucleotides have been introduced to produce modified cells, including CD4T cells, CD8T cells, natural killer T cells, γδ T cells, and progenitor cells, such as haematopoietic stem cells. The modified cells are capable of direct recognition of a cancer cell expressing a NY-ESO-1 antigen by human leukocyte antigen (HLA) class II-restricted binding of the TCR to the NY-ESO-1 antigen expressed by the cancer cell without presentation of the antigen by antigen presenting cells. In embodiments, the NY-ESO-1 antigen is displayed by the tumor cells. Also included is a method for prophylaxis and/or therapy of cancer by administering modified cells that express a recombinant TCR. Methods for making expression vectors and/or cells which express a recombinant TCR and identifying TCRs to make the expression vectors are also included.

Compositions and methods for use of recombinant T cell receptors for direct recognition of tumor antigen

Provided are methods, compositions, recombinant DNA molecules, and kits for cloning T cell receptors (TCRs). The methods facilitate construction of TCR expression libraries from biological samples containing antigen-specific T cells, including but not limited to tumor biopsies, including frozen tumor biopsies. Peripheral T cells that were engineered with library-derived TCR genes show potent therapeutic anti-tumor effects. The method can be performed using any sample that contains T cells, and can be performed with oligoclonal populations of T cells, such as T cells that have infiltrated a tumor. Primer combinations for first strand cDNA synthesis, second strand cDNA synthesis, and for cloning a plurality of distinct TCR β and TCR α chains into a plurality of vectors are provided. Cells containing the vectors are provided, as are kits for use in rapid cloning of the TCR β and TCR α chains.

Compositions and methods for rapid cloning of t-cell receptors

The present disclosure provides antibodies that specifically bind to human glucocorticoid-induced TNFR family related receptor (GITR) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human GITR and modulate GITR activity, e.g., enhance, activate or induce GITR activity, utilizing such antibodies. The present disclosure also provides methods for treating disorders, such as cancer and infectious diseases, by administering an antibody that specifically binds to human GITR and modulates GITR activity e.g., enhances, activates or induces GITR activity.

Anti-GITR antibodies and methods of use thereof

The present disclosure provides multispecific (e.g., bispecific) antibodies that specifically bind to human GITR and/or human OX40 as well as compositions comprising such antibodies. In a specific aspect, the multispecific antibodies specifically bind to human GITR and OX40 and modulate GITR and/or OX40 activity, e.g., enhance, activate, or induce GITR and/or OX40 activity, or reduce, deactivate, or inhibit GITR and/or OX40 activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering a multispecific antibody that specifically binds to human GITR and/or OX40 and modulates GITR and/or OX40 activity, e.g., enhances, activates, or induces GITR and/or OX40 activity. Also provided are methods for treating autoimmune or inflammatory diseases or disorders, by administering a multispecific antibody that specifically binds to human GITR and/or OX40 and modulates GITR and/or OX40 activity, e.g., reduces, deactivates, or inhibits GITR and/or OX40 activity.

Antibodies and methods of use thereof

Provided are compositions and methods for prophylaxis and/or therapy of a variety of cancers which express a NY-ESO-1 antigen. Included are recombinant T cell receptors (TCRs), polynucleotides encoding them, expression vectors that include the polynucleotides, and cells into which the polynucleotides have been introduced to produce modified cells, including CD4T cells, CD8T cells, natural killer T cells, &#x3b3;&#x3b4; T cells, and progenitor cells, such as haematopoietic stem cells. The modified cells are capable of direct recognition of a cancer cell expressing a NY-ESO-1 antigen by human leukocyte antigen (HLA) class II-restricted binding of the TCR to the NY-ESO-1 antigen expressed by the cancer cell without presentation of the antigen by antigen presenting cells. In embodiments, the NY-ESO-1 antigen is displayed by the tumor cells. Also included is a method for prophylaxis and/or therapy of cancer by administering modified cells that express a recombinant TCR. Methods for making expression vectors and/or cells which express a recombinant TCR and identifying TCRs to make the expression vectors are also included.

Provided are recombinant polynucleotides, including expression vectors encoding an alpha chain and/or a beta chain of a TCR having amino acid sequences from any of novel the AL, KQ, PP, 19305CD8, BB, KB, ST, JD, 19305DP, PB-P, PB-T, and PB 13.2 T Cell Receptors (TCRs) that are embodiments of the invention. Cells comprising the polynucleotides are provided, as are libraries of the recombinant polynucleotides and expression vectors. Methods are provided and involve administering to an individual modified human T cells that express a novel recombinant TCR. The methods are for prophylaxis and/or therapy of an individual diagnosed with, suspected of having or at risk for developing or recurrence of a cancer, wherein the cancer includes cancer cells which express NY-ESO-1 and/or its highly homologous LAGE-1 antigen.

Compositions and libraries comprising recombinant T-cell receptors and methods of using recombinant T-cell receptors

Compositions and method for use of recombinant T cell receptors for direct recognition of tumor antigen

Growing community of inventors

Williamsville, NY, United States of America

Takemasa Tsuji