T cell receptors for immunotherapy

A technology of cell receptors and immune cells, applied in the fields of immunology and medicine, can solve the problem of few immunogenic targets

Pending Publication Date: 2020-07-17
BOARD OF RGT THE UNIV OF TEXAS SYST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] While several tumor-associated antigens have been identified for melanoma and a small number of other solid tumor malignancies, there are few immunogenic targets for pancreatic, ovarian, gastric, lung, cervical, breast, and head and neck cancers

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0201] Human SLC45A2 T cell receptor (TCR) clone

[0202] method

[0203] Generation of T cell clones

[0204] TCR clones were generated by exposing cells to specific SLC45A2 peptides. SLC45A2 can be selectively expressed in melanoma compared with normal tissues. SLC45A2 PeptideSLC45A2 382-390 and SLC45A2 393-402 Cytotoxic T lymphocytes (CTL) that selectively bind to immunogenic epitopes of HLA-A*0201 (HLA-A2) and HLA-A*2402 (HLA-A24), respectively, and are expanded using these peptides Can effectively kill a variety of melanoma cells, including a variety of cutaneous melanoma, uveal melanoma, mucosal melanoma and metastatic melanoma. SLC45A2 peptides can exhibit antigen-specific and HLA-A*0201 or HLA A*2402-restricted SLC45A2-specific CD8 T cell responses.

[0205] Full-length VCX3A RNA was transfected into mature dendritic cells (DC). In the presence of IL-21, RNA-transfected DCs were co-cultured with autologous naive T cells at a ratio of DC:T=1:10. After one week...

Embodiment 2

[0226] Functionality of Human SLC45A2 T Cell Receptor (TCR) Clone #39

[0227] Tetramer staining assay of TCR-engineered T cells. The TCR from SLC45A2 CTL (clone #39) was cloned into the retroviral expression vector pMSGV1 and recombinant retroviruses were generated for infection of PBMCs. Following infection, tetrameric+ populations of CD8+ and CD4+ T cells emerged. The CD8+ tetramer+ and CD4+ tetramer+ populations were sorted and amplified using the Rapid Expansion Protocol (REP). After amplification, the CD8+ tetramer+ population was 96% pure ( Figure 8 ). However, the tetramer+ population of CD4+ T cells was lost after REP ( Figure 8 ).

[0228] Peptide binding titration assay of TCR-engineered T cells. T2 cells were pulsed with different concentrations of SLC45A2 peptide (from 10 pg / mL to 10 μg / mL) and treated with 51 Cr mark. CD8+ or CD4+ TCR engineered T cells were used as effector cells and co-cultured with T2 cells. Detected after 4 hours of co-culture 51 ...

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Abstract

Provided are T cell receptors (TCR) and TCR variable regions that can selectively bind SLC45A2. The TCR may be utilized in various therapies, such as autologous cell transplantation, to treat a cancer, such as a cutaneous melanoma, uveal melanoma, a mucosal melanoma, or a metastatic melanoma. Methods for expanding a population of T cells that target SLC45A2 are also provided.

Description

[0001] This application claims the benefit of priority to US Provisional Application Serial No. 62 / 571,447, filed October 12, 2017, the entire contents of which are hereby incorporated by reference. [0002] Incorporation of Sequence Listings [0003] The Sequence Listing contained in the 44.7KB (as measured in Microsoft Windows) file named "UTFCP1314WO.txt" created on October 12, 2018 is submitted by electronic submission and is incorporated herein by reference. [0004] background [0005] 1. Technical field [0006] The present invention relates generally to the fields of immunology and medicine. More specifically, it involves the T cell receptor (TCR). In certain embodiments, the TCRs can be used to treat cancer. [0007] 2. Background technology [0008] T cell-based therapy has shown significant promise as an approach for the treatment of many cancers; unfortunately, this approach has also been hampered by a lack of immunogenic antigenic targets for common cancers and...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/725C12N15/12C12N5/10
CPCA61K35/17C07K14/7051C07K14/435A61K39/00119A61K2039/5156A61K2039/5158C12N5/0636A61K39/001111C12N2510/00A61K31/675A61K31/7076C12N5/0637C12N15/86C07K14/70539
Inventor G·黎姿C·翊
Owner BOARD OF RGT THE UNIV OF TEXAS SYST
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