An Adoptive T Cell Immunotherapy Targeting Cancer Stem Cells in a Colon Cancer Model

Purpose: Colon cancer is one of the most common malignancies worldwide. Cancer stem-like cells (CSCs) are a distinct subgroup of cancer cells that play a vital role in the development of cancer and also a role in the development of resistance against therapeutic agents. In this study we investigated the role of CSCs in colon cancer and evaluated the tumor-associated antigen CEP55 for targeting immunotherapeutically CSCs.

Methods: Side population (SP) cells from colon cancer cell line SW480, were isolated using DNA-binding dye Hoechst 33342. The cytotoxic activity of cytotoxic T lymphocytes (CTL) clone 41 for side population (SP) cells and main population (MP) cells was evaluated using 51Cr release assay. The SP cells, MP cells and presorted cells from the colon cancer cell line were evaluated in NOD/SCID mice.

Results: The isolated SP cells showed resistance to the chemotherapeutic agents irinotecan and oxaliplatin, which suggests that targeting the CSCs can be a better strategy for the treatment of chemotherapy-resistant colon cancer. HLA class I and HLA-A24 in SP cells and MP cells were expressed at the same level. We used CTL clone 41 to corroborate the sensitivity of SP cells to cytotoxic T lymphocyte response. The cytotoxic responses of SP cells were to the same extent as they were in MP cells and pre-sorted cells. Adoptive transfer of CTL clone 41 in immunodeficient mice inhibited SW480-induced tumors, suggesting that this approach can be used for colon cancer immunotherapy.

Conclusion: Our novel findings suggest that colon cancer CSCs are sensitive to CTLs, and CEP55, a tumor-associated antigen, can be successfully used as active immunotherapy for targeting CSCs in colon cancer.