	US 12,005,078 B2
	Genetically engineered drug resistant T cells and methods of using the same
Lawrence S. Lamb, Birmingham, AL (US); H. Trent Spencer, Marietta, GA (US); and G. Yancey Gillespie, Birmingham, AL (US)
Assigned to The UAB Research Foundation, Birmingham, AL (US); Emory University, Atlanta, GA (US); and Children's Healthcare of Atlanta, Inc., Atlanta, GA (US)
Appl. No. 15/756,937
Filed by The UAB Research Foundation, Birmingham, AL (US); Emory University, Atlanta, GA (US); and Children's Healthcare of Atlanta, Inc., Atlanta, GA (US)
PCT Filed Sep. 6, 2016, PCT No. PCT/US2016/050428 § 371(c)(1), (2) Date Mar. 1, 2018, PCT Pub. No. WO2017/041106, PCT Pub. Date Mar. 9, 2017.
Claims priority of provisional application 62/214,071, filed on Sep. 3, 2015.
Prior Publication US 2018/0250337 A1, Sep. 6, 2018
Int. Cl. A61K 35/17 (2015.01); A61K 31/495 (2006.01); A61K 39/00 (2006.01); A61K 45/06 (2006.01); A61P 35/00 (2006.01); C07K 14/715 (2006.01); C07K 14/725 (2006.01); C07K 16/30 (2006.01); C12N 5/0783 (2010.01); C12N 9/12 (2006.01)

CPC A61K 35/17 (2013.01) [A61K 31/495 (2013.01); A61K 39/0011 (2013.01); A61K 39/001104 (2018.08); A61K 39/001106 (2018.08); A61K 39/001109 (2018.08); A61K 39/00111 (2018.08); A61K 39/001112 (2018.08); A61K 39/001113 (2018.08); A61K 39/001119 (2018.08); A61K 39/001122 (2018.08); A61K 39/001124 (2018.08); A61K 39/001126 (2018.08); A61K 39/001129 (2018.08); A61K 39/00115 (2018.08); A61K 39/001151 (2018.08); A61K 39/001164 (2018.08); A61K 39/001166 (2018.08); A61K 39/001168 (2018.08); A61K 39/001171 (2018.08); A61K 39/001174 (2018.08); A61K 39/001181 (2018.08); A61K 39/001182 (2018.08); A61K 39/001188 (2018.08); A61K 39/001189 (2018.08); A61K 39/00119 (2018.08); A61K 39/001193 (2018.08); A61K 39/001195 (2018.08); A61K 45/06 (2013.01); A61P 35/00 (2018.01); C07K 14/7051 (2013.01); C07K 14/7155 (2013.01); C07K 16/30 (2013.01); C12N 5/0636 (2013.01); C12N 5/0638 (2013.01); C12N 5/0646 (2013.01); C12N 9/12 (2013.01); C12Y 207/10001 (2013.01); A61K 2039/5156 (2013.01); A61K 2039/5158 (2013.01); A61K 2300/00 (2013.01); C07K 2319/70 (2013.01); C12N 2501/72 (2013.01); C12N 2510/00 (2013.01)]

30 Claims

1. A method of treating a subject suffering from a tumor, the method comprising:

a. administering to the subject a cell composition comprising γδ T cells expressing at least NKG2D, a chimeric antigen receptor (CAR) directed to a tumor antigen,, and a polypeptide that confers resistance to a chemotherapeutic agent, wherein the chemotherapeutic agent increases the expression of a NKG2D ligand on the tumor; and

b. administering to the subject the chemotherapeutic agent, wherein the chemotherapeutic agent is administered either before administration of the cell composition to the subject, after administration of the cell composition to the subject, concurrently with administration of the cell composition to the subject or any combination of the foregoing;

wherein the CAR comprises an endodomain, and the endodomain consists of a CD3-zeta signaling domain or one costimulatory domain.