Methods of producing enriched populations of tumor-reactive t cells from tumor

An isolated or purified cell population comprising any one or more of:

• (a) CD8+/4-1BB+/PD-1+ T cells,
• (b) CD8+/4-1BB−/PD-1+ T cells,
• (c) CD8+/4-1BB+/PD-1− T cells,
• (d) CD8+/LAG-3+/PD-1+ T cells,
• (e) CD8+/LAG-3−/PD-1+ T cells,
• (f) CD8+/LAG-3+/PD-1− T cells,
• (g) CD8+/TIM-3+/PD-1+ T cells,
• (h) CD8+/TIM-3−/PD-1+ T cells,
• (i) CD8+/TIM-3+/PD-1− T cells,
• (j) CD8+/TIM-3+/LAG-3+ T cells,
• (k) CD8+/TIM-3−/LAG-3+ T cells,
• (1) CD8+/TIM-3+/LAG-3− T cells,
• (m) CD8+/4-1BB+/LAG-3+ T cells,
• (n) CD8+/4-1BB−/LAG-3+ T cells,
• (o) CD8+/4-1BB+/LAG-3− T cells,
• (p) CD8+/4-1BB+/TIM-3+ T cells,
• (q) CD8+/4-1BB−/TIM-3+ T cells, and
• (r) CD8+/4-1BB+/TIM-3− T cells,
• wherein the cell population is enriched for tumor-reactive T cells.

A method of treating cancer using a cell population enriched for tumor-reactive T cells, comprising:

• (a) obtaining a bulk population of T cells from a tumor sample of a cancer patient;
• (b) specifically selecting CD8+ T cells that express any one or more of TIM-3, LAG-3, 4-1BB, and PD-1 from the bulk population;
• (c) separating the cells selected in (b) from unselected cells to obtain a cell population enriched for tumor-reactive T cells;
• and
• (d) administering the cell population enriched for tumor-reactive T cells to the cancer patient.