Compositions and methods of preparing alloreactive cytotoxic T cells
Provided herein are compositions and methods of preparing therapeutic cytotoxic T cells. In certain embodiments, such T cells are generated through activation of donor cells by patient stimulator cells.
1. A composition administrable to a patient, comprising:
alloreactive cytotoxic T cells,
wherein the alloreactive cytotoxic T cells have been produced from cells of a donor that is partially human leukocyte antigen (HLA) disparate with the patient, and
wherein the cytotoxic T cells have been activated to recognize a predetermined cell type in the patient.
2. The composition of claim 1 , wherein the alloreactive cytotoxic T cells have been activated to recognize a predetermined cell type in the patient by displaying alloresponsiveness to HLA determinants present on the patient's cells.
3. The composition of claim 1 , wherein the alloreactive cytotoxic T cells have been activated to recognize peptides derived from HLA.
4. The composition of claim 3 , wherein the alloreactive cytotoxic T cells have been activated to recognize a HLA antigen of the patient.
5. The composition of claim 3 , wherein the alloreactive cytotoxic T cells have been contacted with matured dendritic cells from the patient.
6. The composition of claim 5 , wherein the dendritic cells have been matured by exposure to cytokines with or without one or more pathogen-associated molecular pattern (PAMP) molecules.
7. The composition of claim 5 , wherein the dendritic cells from the patient have been inactivated.
8. The composition of claim 5 , wherein the dendritic cells have been derived from monocytes of the patient.
9. The composition of claim 3 , wherein the patient has cancer.
10. The composition of claim 9 , wherein the cancer is a tumor located in an immune-privileged site.
11. The composition of claim 10 , wherein the tumor is located in the brain.
12. The composition of claim 1 , wherein to recognize a predetermined cell type in the patient comprises to display alloresponsiveness to HLA determinants present on the patient's cells.