Cell immunotherapy for the treatment of cancer
Embodiments of the disclosure encompass compositions comprising immune effector cells, such as natural killer (NK) cells, where the cells comprise one or more exogenously provided interleukins (IL), and wherein the cell optionally comprises one or more engineered receptors. In specific embodiments, the IL is not IL-15, and is IL-12, IL-21, or both. The NK cells may be utilized for treatment of cancer of any kind, including at least glioblastoma.
1 . A composition comprising engineered natural killer (NK) cells, said engineered NK cells expressing one or more secretable heterologous interleukins (IL), wherein the secretable heterologous IL is selected from the group consisting of IL-21, IL-12, IL-2, IL-18, IL-7, and the p35 and p40 subunits of IL-12 artificially linked together with a linker, and wherein the NK cell expresses one or more chimeric antigen receptors (CAR) and/or T cell receptors (TCR) that target B7-H3, EGFRvIII, GD2, IL-13Ra2, CD5, CD70, or PRAME.
2 . The composition of claim 1 , wherein the IL is IL-12, IL-21, IL-18, or a combination thereof.
3 . The composition of claim 1 , wherein said IL is secreted, tethered, or membrane bound in the cell.
4 . The composition of claim 1 , wherein the one or more heterologous IL are expressed from a vector in the engineered NK cells and/or wherein the engineered NK cells are cultured in the presence of one or more IL.
5 . The composition of claim 1 , wherein the engineered NK cell comprises a suicide gene.
6 . The composition of claim 1 , wherein the engineered NK cell is reduced or inhibited in expression of one or more of endogenous genes selected from the group consisting of TDAG8, NKG2A, SIGLEC-7, LAG3, TIM3, CISH, FOXOl, TGFBR2, TIGIT, CD96, ADORA2, NR3C1, PD1, PDL-1, PDL-2, CD47, SIRPA, SHIP1, ADAM 17, RPS6, 4EBP1, CD25, CD40, IL21R, ICAM1, CD95, CD80, CD86, IL10R, CD5, CD7, and a combination thereof.