US 11,883,430 B2
CD38-NAD+ regulated metabolic axis in anti-tumor immunotherapy
Shikhar Mehrotra, Mount Pleasant, SC (US); and Shilpak Chatterjee, Charleston, SC (US)
Assigned to MUSC Foundation for Research Development, Charleston, SC (US)
Appl. No. 16/347,743
Filed by MUSC FOUNDATION FOR RESEARCH DEVELOPMENT, Charleston, SC (US)
PCT Filed Nov. 8, 2017, PCT No. PCT/US2017/060537
§ 371(c)(1), (2) Date May 6, 2019,
PCT Pub. No. WO2018/089423, PCT Pub. Date May 17, 2018.
Claims priority of provisional application 62/419,612, filed on Nov. 9, 2016.
Prior Publication US 2019/0255111 A1, Aug. 22, 2019
Int. Cl. A61K 35/17 (2015.01); A61P 35/00 (2006.01); A61K 35/26 (2015.01); C07K 16/24 (2006.01); C12N 5/0783 (2010.01); A61K 45/06 (2006.01); A61K 9/00 (2006.01); C07K 16/28 (2006.01); C07K 16/30 (2006.01); A61K 39/395 (2006.01)
CPC A61K 35/17 (2013.01) [A61K 9/0019 (2013.01); A61K 35/26 (2013.01); A61K 39/39558 (2013.01); A61K 45/06 (2013.01); A61P 35/00 (2018.01); C07K 16/249 (2013.01); C07K 16/2896 (2013.01); C07K 16/30 (2013.01); C12N 5/0636 (2013.01); C12N 5/0638 (2013.01); C07K 2317/55 (2013.01); C07K 2317/76 (2013.01); C12N 2501/15 (2013.01); C12N 2501/2301 (2013.01); C12N 2501/2306 (2013.01); C12N 2501/2312 (2013.01); C12N 2501/2323 (2013.01); C12N 2501/599 (2013.01)] 14 Claims
 
1. An ex vivo method for producing hybrid Th1/Th17 and/or Tc1/Tc17 cells comprising:
(a) obtaining a starting population of T cells comprising CD4+ and CD8+ T cells; and
(b) culturing the starting population of T cells in the presence of recombinant IL6, IL1β, IL23, TGFβ and IL-12, thereby differentiating the starting population of T cells to hybrid Th1/Th17 and/or Tc1/Tc17 cells,
wherein the TGFβ is present at a concentration of 0.1 to 0.5 ng/mL, the IL1β, IL23, IL6, and IL12 are each present at a concentration of 5 to 30 ng/mL.