	US 12,358,967 B2
	Methods of obtaining tumor-specific T cell receptors
Xiangjun Zhou, Shenzhen (CN); Yanyan Han, Shenzhen (CN); and Xihe Chen, Shenzhen (CN)
Assigned to HRYZ (SHANGHAI) BIOTECH CO., Shanghai (CN); and HRYZ (GUANGZHOU) BIOTECH CO., Guangzhou (CN)
Filed by SYZ Cell Therapy Co., Guangdong (CN); and HRYZ Biotech Co., Guangdong (CN)
Filed on Jun. 17, 2022, as Appl. No. 17/843,916.
Application 17/843,916 is a division of application No. 17/047,059, granted, now 11,390,659, previously published as PCT/CN2019/082408, filed on Apr. 12, 2019.
Prior Publication US 2022/0402999 A1, Dec. 22, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 35/17 (2025.01); A61K 40/11 (2025.01); A61K 40/19 (2025.01); A61K 40/24 (2025.01); A61K 40/32 (2025.01); A61K 40/42 (2025.01); A61K 40/46 (2025.01); A61P 35/00 (2006.01); C07K 14/725 (2006.01); C12N 5/078 (2010.01); C12N 5/0783 (2010.01); C12N 5/0784 (2010.01); C12N 5/22 (2006.01); C12P 21/02 (2006.01); A61K 38/00 (2006.01)

CPC C07K 14/7051 (2013.01) [A61K 40/11 (2025.01); A61K 40/19 (2025.01); A61K 40/24 (2025.01); A61K 40/32 (2025.01); A61K 40/4201 (2025.01); A61K 40/4205 (2025.01); A61K 40/4208 (2025.01); A61K 40/4232 (2025.01); A61K 40/4239 (2025.01); A61K 40/424 (2025.01); A61K 40/4241 (2025.01); A61K 40/4243 (2025.01); A61K 40/4246 (2025.01); A61K 40/4266 (2025.01); A61K 40/4268 (2025.01); A61K 40/4269 (2025.01); A61K 40/46 (2025.01); A61P 35/00 (2018.01); C12N 5/0636 (2013.01); C12N 5/0639 (2013.01); C12P 21/02 (2013.01); A61K 38/00 (2013.01); C12N 2502/1114 (2013.01); C12N 2502/1121 (2013.01)]

20 Claims

1. A method of treating a cervical cancer comprising RGS5 in an individual, comprising intravenously administering to the individual an effective amount of a pharmaceutical composition comprising an engineered immune cell comprising a tumor-specific T-cell receptor (TCR) and a pharmaceutically acceptable carrier, wherein the TCR binds to an epitope of RGS5 comprising the amino acid sequence of SEQ ID NO: 82 or SEQ ID NO: 83, wherein the engineered immune cell is from the same individual, and wherein the TCR is selected from the group consisting of the following TCRs:

(a) a TCR comprising a TCRα chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 254, a CDR2 comprising the amino acid sequence of SEQ ID NO: 255, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 28; and a TCRβ chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 256, a CDR2 comprising the amino acid sequence of SEQ ID NO: 257, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 31;

(b) a TCR comprising a TCRα chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 258, a CDR2 comprising the amino acid sequence of SEQ ID NO: 259, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and a TCRβ chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 260, a CDR2 comprising the amino acid sequence of SEQ ID NO: 261, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 37;

(c) a TCR comprising a TCRα chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 262, a CDR2 comprising the amino acid sequence of SEQ ID NO: 263, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 40; and a TCRβ chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 264, a CDR2 comprising the amino acid sequence of SEQ ID NO: 265, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 43;

(d) a TCR comprising a TCRα chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 266, a CDR2 comprising the amino acid sequence of SEQ ID NO: 267, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 46; and a TCRβ chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 268, a CDR2 comprising the amino acid sequence of SEQ ID NO: 269, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 49; and

(e) a TCR comprising a TCRα chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 270, a CDR2 comprising the amino acid sequence of SEQ ID NO: 271, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 52; and a TCRβ chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 272, a CDR2 comprising the amino acid sequence of SEQ ID NO: 273, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 55.