Enhancing car-t cell performance for cancer immunotherapy

2:

• The genetically modified CD8 cell or CAR-T cell of claim 1, wherein the CD8 cell or CAR-T cell is formulated as a pharmaceutical, or formulated for in vivo administration.

3:

• A CD8 cell or CAR-T cell or a pharmaceutical formulation comprising a CAR-T cell, wherein the CAR-T cell comprises or has contained therein a compound or composition capable of generating a phenotype of:
• increased expression of, or substantially increased expression or activity of, or more than wild type levels of expression or activity of, a decaprenyl-diphosphate synthase subunit 2 (PDSS2) enzyme or gene.

4:

• The CD8 cell or CAR-T cell of claim 1, wherein the CD8 cell or CAR-T cell further comprises, or has implanted, a heterologous nucleic acid encoding a protein having decaprenyl-diphosphate synthase subunit 2 (PDSS2) enzyme function.

5:

• The CD8 cell or CAR-T cell of claim 1, wherein the PDSS2 enzyme or gene is a human enzyme or gene.

7:

• The CD8 cell or CAR-T cell of claim 1, further comprising an expression vehicle or a vector having the heterologous nucleic acid contained therein, and the heterologous nucleic acid expresses a PDSS2 enzyme in the CD8 cell or CAR-T cell.

8:

• The CD8 cell or CAR-T cell of claim 7, wherein the expression vehicle or the vector is or comprises an expression construct, a plasmid, an expression vehicle, or a virus.

10:

• The CD8 cell or CAR-T cell of claim 1, wherein the PDSS2 enzyme-expressing nucleic acid is an RNA or a DNA molecule, or a synthetic nucleic acid.

11:

• The CD8 cell or CAR-T cell of claim 1, wherein the CAR-T cell is formulated or manufactured as or with a pharmaceutical, an implant, a device or is formulated for in vivo administration.

12:

• A product of manufacture or kit, or a pharmaceutical formulation, comprising a CD8 cell or CAR-T cell of claim 1.

13:

• A method for metabolically enhancing a CD8 T cell or a CAR-T cell resulting in the CD8 T cell or the CAR-T having improved metabolic fitness, and metabolically enhancing chimeric antigen receptor (CAR)-T cell function and persistence in vitro or in vivo, the method comprising inserting in the CD8 T cell or the CAR-T cell or transfecting the CD8 T cell or the CAR-T cell a heterologous nucleic acid encoding a protein having decaprenyl-diphosphate synthase subunit 2 (PDSS2) enzyme function.

14:

• The method of claim 13, wherein the PDSS2 enzyme has a sequence as set forth in any of SEQ ID NO:1 to SEQ ID NO:15, or the heterologous nucleic acid encodes a protein having an amino acid sequence as set forth in any of SEQ ID NO:
• 1 to SEQ ID NO:
• 15.

15:

• The method of claim 13, wherein the heterologous nucleic acid encoding the protein having PDSS2 enzyme function is contained in an expression vehicle or a vector.

16:

• The method of claim 15, wherein the expression vehicle, vector or virus is or is derived from:
• a herpes simplex virus, a human immunodeficiency virus (HIV), a synthetic vector, an adeno-associated virus (AAV), a lentivirus, an adenovirus or a plasmid.

18:

• The method of claim 17, wherein the CD8 cell or CAR-T cell is administered by intravenous injection, subcutaneous injection, intrathecal injection, or intramuscular injection.

19:

• The method of claim 17, wherein between about 102 and 1010 CD8 cells or CAR-T cells are administered to the individual in need thereof.

20-21. (canceled)

22:

• The method of claim 17, wherein in step (a):
• (i) the CD8 cell or CAR-T cell has increased expression of nucleic acids encoding PDSS2, or
• (ii) the CAR-T cell is contacted with nucleic acids encoding PDSS2 before in vivo administration to an individual in need thereof, during or with in vivo administration of the CD8 cell or CAR-T cell, and/or after in vivo administration of the CD8 cell or CAR-T cell.

23:

• The method of claim 17, wherein in step (b) the CD8 cell or CAR-T cell has increased expression of nucleic acids encoding PDSS2.