Some interesting info from one of the patents (program four), as it seems both the (CAR) NK cells and (CAR) T-cells will use an OX40 co-stim and mbIL-15 (I don't know about the ex vivo expansion of the T-cells).
Also, the NK cells do not express a detectable level of CIS protein.
The NK cells are further genetically engineered to express a reduced level of a transforming growth factor beta receptor.
The NK cells are further genetically edited to express a reduced level of B2M.
The NK cells are further genetically edited to express a reduced level of CIITA.
The NK cells are further genetically edited to express a reduced level of NKG2A receptor.
The NK cells are further genetically edited to express a reduced level of a Cbl proto-oncogene B protein encoded by a CBLB gene.
The NK cells are further genetically edited to express a reduced level of a tripartite motif-containing protein 29 protein encoded by a TRIM29 gene.
The NK cells are further genetically edited to express a reduced level of a suppressor of cytokine signaling 2 protein encoded by a SOCS2 gene.
The NK cells are further genetically edited to express CD47.
The NK cells are further genetically engineered to express HLA-E.
The NK cells are further genetically edited to disrupt expression of at least one immune checkpoint protein by the NK cells (CTLA4, PD-1, LAG-3, NKG2A receptor, KIR2DL-1, KIR2DL-2, KIR2DL-3, KIR2DS-1 and/or KIR2DA-2, and combinations thereof).
Moving on,
The T-cells comprise at least one genetically edited subunit of a TCR (alpha), or TCR KO, such that they do not exhibit alloreactive effects against cells of a recipient subject.
The T-cells are further genetically edited to reduce expression of one or more of CIS, TGFBR, B2M, and CIITA as compared to non-engineered T cells, or to express CD47 or HLA-E.
The T-cells are further genetically edited to reduce expression of one or more of TRIM29 and SOCS2.
The T-cells are further genetically edited to disrupt expression of at least one immune checkpoint protein, wherein the at least one immune checkpoint protein is selected from CTLA4, PD-1, and LAG-3.
