Health Research, Inc.

Kunle Odunsi

Takemasa Tsuji

Junko Matsuzaki

Richard Koya

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

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.

Growing community of inventors

Williamsville, NY, United States of America

Kunle Odunsi