Compositions and methods for immune cell modulation in adoptive immunotherapies

A method of modulating a population of immune cells, comprising:

• contacting the immune cells with a sufficient amount of a composition comprising at least one agent for a time sufficient to obtain a population of modulated immune cells having improved therapeutic potential in comparison to unmodulated immune cells, wherein (a) the population of immune cells comprises T cells or NK cells;
• and (b) the at least one agent is selected from the group consisting of:
• Dorsomorphin;
• Heptelidic acid, 1-Pyrrolidinecarbodithioic acid, ammonium salt;
• 2-deoxyglucose (2-DG);
• GSK3 Inhibitors;
• Rho kinase inhibitors;
• MEK inhibitors, PDK1 agonists;
• TGFβ inhibitors;
• 6-Mercaptopurine;
• AC-93253 iodide;
• Tiratricol;
• PI-103;
• Fulvestrant;
• Thapsigargin;
• SU 4312;
• Telmisartan;
• Cyclosporin A;
• 1,3,5-tris(4-hydroxyphenol)-4-propyl-1H-pyrazole;
• BAY 61-3606;
• Protoporphyrin IX disodium;
• mTOR inhibitors;
• HS173;
• LY294002, Pictilisib;
• 5-Azacytidine;
• Fludarabine;
• Roscovitine, (S)-Isomer;
• PAC-1;
• 8-Quinolinol, 5,7-dichloro-;
• Nitrofurantoin;
• 8-Quinolinol, 5-chloro-7-iodo-;
• 2-Naphthacenecarboxamide, 7-chloro-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahy, Nifuroxazide;
• Tosufloxacin hydrochloride;
• Sertralin;
• Diethylenetriaminepentaacetic acid, penta sodium;
• Edrophonium chloride;
• BIX01294;
• Terfenadine;
• dmPGE2 (16,16-dimethyl Prostaglandin E2);
• and analogues thereof;
• and further wherein;
• (i) the immune cells are genetically modified to comprise an insertion, a deletion, or a nucleic acid replacement;
• or
• (ii) the method further comprises administering the modulated immune cells to a subject, wherein the modulated immune cells are autologous or allogeneic;
• and wherein the subject has an autoimmune disorder, a hematological malignancy, a solid tumor, cancer, or an infection associated with HIV, RSV, EBV, CMV, adenovirus, or BK polyomavirus.