Health Research, Inc.

Junko Matsuzaki

Takemasa Tsuji

Kunle Odunsi

Adekunle Odunsi

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 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.

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Williamsville, NY, United States of America

Junko Matsuzaki