Cd28 t cell cultures, compositions, and methods of using thereof

A method for producing T cells with improved efficacy for adoptive immunotherapy comprising

• obtaining starting PBMCs from a patient or a donor,
• determining a % of CD28+ CD8+ T cells in the starting PBMCs, and
• activating the determined starting PBMCs with anti-CD3 antibody and anti-CD28 antibody, provided that the determined starting PBMCs comprises at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% of CD28+ CD8+ T cells, or
• activating the determined starting PBMCs with anti-CD3 antibody in the absence of anti-CD28 antibody, provided that the determined starting PBMCs comprises less than about 50%, less than about 45%, less than about 40%, less than about 35%, less than about 30%, less than about 25%, less than about 20%, less than about 15%, less than about 10%, less than about 9%, less than about 8%, less than about 7%, less than about 6%, less than about 5%, less than about 4%, less than about 3%, less than about 2%, or less than about 1% of CD28+ CD8+ T cells.

A method of treating a patient who has cancer, comprising

• obtaining starting peripheral blood mononuclear cells (PBMCs) from the patient,
• determining a % of CD28+ CD8+ T cells in the starting PBMCs,
• activating the determined starting PBMCs with anti-CD3 antibody in the absence of anti-CD28 antibody, provided that the determined starting PBMCs comprises less than about 50%, less than about 45%, less than about 40%, less than about 35%, less than about 30%, less than about 25%, less than about 20%, less than about 15%, less than about 10%, less than about 9%, less than about 8%, less than about 7%, less than about 6%, less than about 5%, less than about 4%, less than about 3%, less than about 2%, or less than about 1% of CD28+ CD8+ T cells,
• transducing T cells from the activated starting PBMCs with a viral vector,
• expanding the transduced T cells, and
• administering to the patient the expanded T cells,
• wherein the cancer is selected from the group consisting of hepatocellular carcinoma (HCC), colorectal carcinoma (CRC), glioblastoma (GB), gastric cancer (GC), esophageal cancer, non-small cell lung cancer (NSCLC), pancreatic cancer (PC), renal cell carcinoma (RCC), benign prostate hyperplasia (BPH), prostate cancer (PCA), ovarian cancer (OC), melanoma, breast cancer, chronic lymphocytic leukemia (CLL), Merkel cell carcinoma (MCC), small cell lung cancer (SCLC), Non-Hodgkin lymphoma (NHL), acute myeloid leukemia (AML), gallbladder cancer and cholangiocarcinoma (GBC, CCC), urinary bladder cancer (UBC), acute lymphoblastic leukemia (ALL), multiple myeloma (MM), and uterine cancer (UEC).