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; (ii) tumor-reactive T lymphocytes and/or natural killer cells within the pores, (iii) a peptide having the sequence of SEQ ID NO: 2; and (iv) at least one antibody selected from an anti-CD3 antibody, an anti-CD28 antibody, and an anti-CD137 antibody.
2. An ex vivo implantable composition of claim 1 , wherein the at least one antibody is bound to or incorporated in one or more particles within the composition.
3. An ex vivo implantable composition of claim 2 , wherein the particles are embedded in the pores of the scaffold and comprise pores with a diameter of about 100 Å.
4. An ex vivo implantable composition of claim 2 , wherein the particles are porous silica microparticles.
5. An ex vivo implantable composition of claim 1 , wherein the peptide having the sequence of SEQ ID NO: 2 is associated with the porous scaffold in a bioactive coating on the porous scaffold.
6. An ex vivo implantable composition of claim 5 , wherein the bioactive coating comprises anti-CD28 antibodies.
7. An ex vivo implantable composition of claim 5 , wherein the bioactive coating comprises anti-CD3 antibodies.
8. An ex vivo implantable composition of claim 5 , wherein the bioactive coating comprises anti-CD137 antibodies.
9. An ex vivo implantable composition of claim 1 , further comprising a cytokine.
10. An ex vivo implantable composition of claim 9 , wherein the cytokine is interleukin-15.
11. A method of treating a tumor in a subject comprising implanting a composition of claim 1 into a subject within a proximity to a tumor cell sufficient to lead to the destruction of the tumor cell in the subject, thereby treating the tumor.
12. A method of claim 11 , wherein the implanting is within a tumor resection bed.
13. An ex vivo implantable composition comprising (i) a porous scaffold comprising pores; (ii) tumor-reactive T lymphocytes and/or natural killer cells within the pores, (iii) a cytokine; and (iv) at least one antibody selected from an anti-CD3 antibody, an anti-CD28 antibody, and an anti-CD137 antibody.
14. An ex vivo implantable composition of claim 13 , further comprising a peptide having the sequence of SEQ ID NO: 2.
15. An ex vivo implantable composition of claim 14 , wherein the peptide having the sequence of SEQ ID NO: 2 is associated with the porous scaffold in a bioactive coating on the porous scaffold.
16. An ex vivo implantable composition of claim 13 , wherein the cytokine is interleukin-15.
17. An ex vivo implantable composition of claim 13 , wherein the at least one antibody is bound to or incorporated in one or more particles within the composition.
18. An ex vivo implantable composition of claim 17 , wherein the particles are embedded in the pores of the scaffold and comprise pores with a diameter of about 100 Å.
19. A method of treating a tumor in a subject comprising implanting a composition of claim 13 into a subject within a proximity to a tumor cell sufficient to lead to the destruction of the tumor cell in the subject, thereby treating the tumor.
20. A method of claim 19 , wherein the implanting is within a tumor resection bed.