	US 12,144,826 B2
	Methods of treating EGFRvIII expressing glioblastomas
Wendell A. Lim, San Francisco, CA (US); Hideho Okada, San Francisco, CA (US); Kole T. Roybal, San Francisco, CA (US); Joseph H. Choe, San Francisco, CA (US); and Payal B. Watchmaker, San Francisco, CA (US)
Assigned to THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, Oakland, CA (US)
Appl. No. 17/042,030
Filed by The Regents of the University of California, Oakland, CA (US)
PCT Filed Apr. 4, 2019, PCT No. PCT/US2019/025846 § 371(c)(1), (2) Date Sep. 25, 2020, PCT Pub. No. WO2019/195586, PCT Pub. Date Oct. 10, 2019.
Claims priority of provisional application 62/654,012, filed on Apr. 6, 2018.
Claims priority of provisional application 62/722,681, filed on Aug. 24, 2018.
Prior Publication US 2021/0023138 A1, Jan. 28, 2021
Int. Cl. A61K 35/17 (2015.01); A61P 35/00 (2006.01); C07K 14/71 (2006.01); C07K 14/725 (2006.01)

CPC A61K 35/17 (2013.01) [A61P 35/00 (2018.01); C07K 14/7051 (2013.01); C07K 14/71 (2013.01)]

8 Claims

1. A method of treating a subject for an epidermal growth factor receptor variant III (EGFRvIII) positive glioblastoma, the method comprising:

administering to the subject an immune cell genetically modified with:

(a) a nucleic acid sequence encoding a binding triggered transcriptional switch (BTTS) that binds to EGFRvIII;

(b) a nucleic acid sequence encoding a tandem chimeric antigen receptor (CAR) or a T cell receptor (TCR), wherein the tandem CAR or TCR comprises a first binding domain that recognizes Ephrin type-A receptor 2 (EphA2) and a second binding domain that recognizes IL-13 receptor α2 (IL-13Rα2); and

wherein binding of the BTTS to EGFRvIII on EGFRvIII positive glioblastoma cells activates expression of the tandem CAR or TCR, which binds to EphA2 and/or IL-13Rα2 in the EGFRvIII positive glioblastoma and induces killing of tumor cells in the EGFRvIII positive glioblastoma.