Methods of using IL-21 for adoptive immunotherapy and identification of tumor antigens
Methods for preparing ex vivo T cell cultures using IL- 21 compositions for use in adoptive immunotherapy are described. Addition of IL- 21 to cultures of non-terminally differentiated T cells population, either isolated or present in peripheral blood mononuclear cells are exposed to one or more tumor antigens, and in the presence of IL- 21 compositions and antigen presenting cells (APCs), the resulting T cell population has an enhanced antigen-specificity, and can be reintroduced into the patient. Methods are also disclosed for identifying tumor antigens by culturing T cell populations exposed to IL- 21 compositions and APCs in the presence of tumor material.
1. A method of preparing a T cell population comprising:
obtaining the T cell population from PBMCs;
activating the obtained T cell population,
transducing the activated T cell population with a viral vector comprising a nucleic acid encoding a protein,
expanding the transduced T cell population, and
wherein the activating, transducing, and expanding are performed in the presence of IL-21.
2. The method of claim 1 , wherein the PBMCs are obtained from a patient or a healthy donor.
3. The method of claim 1 , wherein the activating, transducing, and expanding are further performed in the presence of at least one cytokine selected from IL2, IL-12, and IL15.
4. The method of claim 1 , wherein the protein is a T cell receptor.
5. The method of claim 1 , further comprising restimulating the expanded transduced T cell population.
6. The method of claim 5 , wherein the restimulating is performed in the presence of a feeder cell and an anti-CD3 antibody.
7. The method of claim 6 , wherein the feeder cell is an irradiated allogenic feeder cell.
8. The method of claim 7 , wherein the feeder cell comprises a PBL and a LCL.
9. The method of claim 8 , further comprising culturing the restimulated cells in the presence of IL-2.