Compositions and methods for delivery of immune cells to treat un-resectable or non-resected tumor cells and tumor relapse
The present disclosure provides compositions and methods for the delivery of immune cells to treat un-resectable or non-resected tumor cells and tumor relapse. The compositions comprise (i) a structure comprising an injectable polymer or scaffold comprising pores; (ii) lymphocytes disposed within the structure, (iii) at least one lymphocyte-adhesion moiety associated with the structure; and (iv) at least one lymphocyte-activating moiety associated with the structure, and optionally an immune stimulant.
1. An ex vivo implantable composition comprising (i) a porous scaffold comprising pores; (ii) tumor reactive lymphocytes within the pores; and (iii) at least one antibody selected from an anti-CD3 antibody, an anti-CD28 antibody, and an anti-CD137 antibody.
2. The ex vivo implantable composition of claim 1 , wherein the porous scaffold comprises collagen.
3. The ex vivo implantable composition of claim 1 , wherein the tumor-reactive lymphocytes are genetically modified.
4. The ex vivo implantable composition of claim 3 , wherein the genetically-modified tumor-reactive lymphocytes are genetically modified to express a chimeric antigen receptor (CAR), an αβ T cell receptor (TCR), or a proinflammatory cytokine.
5. The ex vivo implantable composition of claim 1 , wherein the tumor-reactive lymphocytes are T cells or NK cells.
6. The ex vivo implantable composition of claim 5 , wherein the T cells or NK cells are genetically-modified to express a CAR.
7. The ex vivo implantable composition of claim 1 , wherein the at least one antibody comprises the anti-CD3 antibody.
8. The ex vivo implantable composition of claim 1 , wherein the at least one antibody comprises the anti-CD28 antibody.
9. The ex vivo implantable composition of claim 1 , wherein the at least one antibody comprises the anti-CD3 antibody and the anti-CD28 antibody.
10. The ex vivo implantable composition of claim 1 , wherein the at least one antibody is covalently bound to the porous scaffold.
11. The ex vivo implantable composition of claim 1 , further comprising an immune stimulant.
12. The ex vivo implantable composition of claim 11 , wherein the immune stimulant comprises a cytokine, an antibody, or a vaccine adjuvant.
13. The ex vivo implantable composition of claim 12 , wherein the cytokine is an interleukin.
14. The ex vivo implantable composition of claim 13 , wherein the interleukin is interleukin-18, interleukin-2, interleukin-12, interleukin-15, and/or interleukin-21.
15. The ex vivo implantable composition of claim 11 , wherein the immune stimulant comprises a Toll-like receptor ligand.
16. The ex vivo implantable composition of claim 11 , wherein the immune stimulant comprises CpG, Poly(I:C), α-galactoceramide, a cyclic dinucleotide, or 17-dimethylaminoethylamino-17-demethoxygeldanamycin.
17. A method of treating cancer in a subject in need thereof comprising implanting the ex vivo implantable composition of claim 1 into an anatomical site within the subject in need thereof thereby treating cancer in the subject in need thereof.
18. The method of claim 17 , wherein the anatomical site is a tumor site.
19. The method of claim 17 , wherein the anatomical site is a tumor resection site.