Methods of treating cancer using cell based therapies

A method of treating a cancer in a subject, said method comprising:

• (i) purifying T cells from the subject providing isolated anergic T cells, wherein the isolated anergic T cells are CD28−CD27− T cells;
• (ii) culturing the isolated CD28−CD27− anergic T cells in a medium containing an effective amount of anti-CD3 antibodies and anti-CD28 antibodies in combination with a phosphatidylinositol-3-kinase inhibitor and a vasoactive intestinal peptide (VIP) receptor antagonist for a sufficient time to produce CD28+CD27+ replicated T cells having increased expression of CD28 compared with levels prior to replication;
• and
• (iii) administering an effective amount of the CD28+CD27+ replicated T cells from step (ii) to the subject, thereby treating the cancer, and wherein the cancer is leukemia or lymphoma.