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

Patent metadata

Field	Value
Publication number	US-10000546-B2
Application number	US-201414774723-A
Country	US
Kind code	B2
Filing date	Mar 13, 2014
Priority date	Mar 13, 2013
Publication date	Jun 19, 2018
Grant date	Jun 19, 2018

Abstract

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 CD4 + T cells, CD8 + T 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.

First claim

We claim:

1. A modified human T cell comprising a recombinant polynucleotide encoding a T cell receptor (TCR), wherein the recombinant polynucleotide encodes a TCR alpha chain having the sequence of SEQ ID NO:3 and a TCR beta chain having the sequence of SEQ ID NO:4, wherein the T cell is capable of direct recognition of a cancer cell expressing a NY-ESO-1 antigen, wherein the direct recognition of the cancer cell comprises human leukocyte antigen (HLA) class II-restricted binding of the TCR to the NY-ESO-1 antigen expressed by the cancer cell.

2. The modified cell of claim 1 , wherein the sequence encoding the alpha chain and/or the beta chain does not comprise introns.

3. An expression vector encoding a T cell receptor (TCR), wherein the TCR comprises an alpha chain having the sequence of SEQ ID NO:3 and a beta chain having the sequence of SEQ ID NO:4.

Assignees

• Health Research Inc

Inventors

• Odunsi Kunle
• Matsuzaki Junko
• Tsuji Takemasa

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/04

  Immunostimulants · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C12N2740/13041

  Use of virus, viral particle or viral elements as a vector · CPC title

• C07K2319/50

  containing protease site · CPC title