US 12,227,554 B2
Methods for selectively expanding cells expressing a TCR with a murine constant region
Drew C. Deniger, Houston, TX (US); Steven A. Feldman, Redwood City, CA (US); and Steven A. Rosenberg, Potomac, MD (US)
Assigned to The United States of America, as represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US)
Appl. No. 16/652,948
Filed by The United States of America,as represented by the Secretary,Department of Health and Human Services, Bethesda, MD (US)
PCT Filed Sep. 24, 2018, PCT No. PCT/US2018/052432
§ 371(c)(1), (2) Date Apr. 1, 2020,
PCT Pub. No. WO2019/070435, PCT Pub. Date Apr. 11, 2019.
Claims priority of provisional application 62/568,339, filed on Oct. 5, 2017.
Prior Publication US 2020/0254018 A1, Aug. 13, 2020
Int. Cl. C07K 14/725 (2006.01); A61K 39/00 (2006.01); C12N 5/0783 (2010.01)
CPC C07K 14/7051 (2013.01) [A61K 39/4611 (2023.05); A61K 39/4632 (2023.05); A61K 39/464406 (2023.05); A61K 39/464451 (2023.05); A61K 39/464491 (2023.05); C12N 5/0636 (2013.01); A61K 2239/28 (2023.05); C12N 2501/2301 (2013.01); C12N 2501/2307 (2013.01); C12N 2501/2312 (2013.01); C12N 2501/2315 (2013.01); C12N 2501/2321 (2013.01); C12N 2501/515 (2013.01); C12N 2510/00 (2013.01)] 17 Claims
 
1. A method of selectively expanding a number of T cells, the method comprising:
modifying human T cells to express a TCR, wherein the TCR comprises a murine constant region;
producing a population of cells comprising a number of the human T cells expressing the TCR and a number of the human T cells not expressing the TCR;
culturing the population of cells in a first culture,
wherein the first culture comprises (i) a first population of irradiated feeder cells, (ii) one or more cytokines, and (iii) a first antibody, or an antigen-binding portion thereof, wherein the first antibody, or antigen-binding portion thereof, specifically binds to the murine constant region of the TCR,
wherein the first culture lacks a second antibody, or an antigen binding portion thereof, which specifically binds to the human CD3 complex, and
wherein the first culture selectively expands the number of human T cells expressing the TCR over the number of human T cells not expressing the TCR.