US 11,896,614 B2
Methods for improving the efficacy and expansion of chimeric antigen receptor-expressing cells
David M. Barrett, Philadelphia, PA (US); Felipe Bedoya, Melrose, MA (US); Saba Ghassemi, Philadelphia, PA (US); Carl H. June, Merion Station, PA (US); Bruce L. Levine, Cherry Hill, NJ (US); Jan J. Melenhorst, Moreland Hills, OH (US); Michael C. Milone, Moorestown, NJ (US); Daniel J. Powell, Jr., Bala Cynwyd, PA (US); Nathan Amar Singh, Philadelphia, PA (US); and Zoe Zheng, Cherry Hill, NJ (US)
Assigned to Novartis AG, Basel (CH); and The Trustees of the University of Pennsylvania, Philadelphia, PA (US)
Appl. No. 15/567,156
Filed by Novartis AG, Basel (CH); and The Trustees of the University of Pennsylvania, Philadelphia, PA (US)
PCT Filed Apr. 15, 2016, PCT No. PCT/US2016/027751
§ 371(c)(1), (2) Date Oct. 17, 2017,
PCT Pub. No. WO2016/168595, PCT Pub. Date Oct. 20, 2016.
Claims priority of provisional application 62/149,249, filed on Apr. 17, 2015.
Prior Publication US 2018/0133296 A1, May 17, 2018
Int. Cl. A61K 35/17 (2015.01); C07K 14/47 (2006.01); C07K 14/705 (2006.01); A61K 38/50 (2006.01); A61K 45/06 (2006.01); C07K 16/28 (2006.01); C12N 5/0783 (2010.01); C07K 14/725 (2006.01); A61K 39/00 (2006.01)
CPC A61K 35/17 (2013.01) [A61K 38/50 (2013.01); A61K 45/06 (2013.01); C07K 14/4748 (2013.01); C07K 14/705 (2013.01); C07K 14/7051 (2013.01); C07K 14/70517 (2013.01); C07K 14/70578 (2013.01); C07K 16/28 (2013.01); C07K 16/2803 (2013.01); C12N 5/0636 (2013.01); C12Y 305/01001 (2013.01); A61K 2039/5156 (2013.01); A61K 2039/5158 (2013.01); C07K 2317/622 (2013.01); C07K 2319/00 (2013.01); C07K 2319/03 (2013.01); C07K 2319/33 (2013.01); C12N 2501/2302 (2013.01); C12N 2501/2305 (2013.01); C12N 2501/2307 (2013.01); C12N 2501/2318 (2013.01)] 15 Claims
 
1. A method of making an immune effector cell population comprising an immune effector cell comprising a chimeric antigen receptor (“CAR”), comprising acquiring a human immune effector cell population from a pediatric subject having a leukemia, wherein the subject has not been treated with cyclophosphamide or cytarabine,
thereby making an immune effector cell population suitable for use in a CAR therapy, wherein the acquired immune effector cell population includes:
(a) one or more of at least 20% naïve T cells, at least 2% stem central memory T cells, and at least 4% central memory T cells;
(b) at least 50% central memory T cells;
(c) less than 55% effector memory and terminal effector T cells combined; or
(d) two or more of (a), (b) and (c), wherein the combined percentages of the two or more of (a), (b), and (c) do not yield a percentage that exceeds 100%; and
wherein the method further comprises introducing into the immune effector cell population a nucleic acid encoding a CAR; and
wherein the immune effector cell population shows an increase in one or more of: (i) ex-vivo expansion of the immune effector cell population, (ii) the efficacy of the immune effector cell population for therapy, or (iii) the yield of the immune effector cell population, relative to a population of immune effector cells acquired from a pediatric subject having a leukemia who has been treated with cyclophosphamide or cytarabine.