T lymphocytes derived from human cord blood provide effective antitumor immunotherapy against a human tumor
1 Transplantation Research Center, Samsung Biomedical Research Institute. Graduate School of Life Science and Biotechnology, CHA University, Seoul, Republic of Korea
2 National Cancer Center Research Institute. Graduate School of Life Science and Biotechnology, CHA University, Seoul, Republic of Korea
3 Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea
BMC Cancer 2011, 11:225 doi:10.1186/1471-2407-11-225Published: 7 June 2011
Although the graft-versus-tumor (GVT) effect of donor-derived T cells after allogeneic hematopoietic stem cell transplantation has been used as an effective adoptive immunotherapy, the antitumor effects of cord blood (CB) transplantation have not been well studied.
We established the animal model by transplantation of CB mononuclear cells and/or tumor cells into NOD/SCID mice. The presence of CB derived T cells in NOD/SCID mice or tumor tissues were determined by flow cytometric and immunohistochemical analysis. The anti-tumor effects of CB derived T cells against tumor was determined by tumor size and weight, and by the cytotoxicity assay and ELISPOT assay of T cells.
We found dramatic tumor remission following transfer of CB mononuclear cells into NOD/SCID mice with human cervical tumors with a high infiltration of CD3+ T cells in tumors. NOD/SCID mice that receive neonatal CB transplants have reconstituted T cells with significant antitumor effects against human cervical and lung tumors, with a high infiltration of CD3+ T cells showing dramatic induction of apoptotic cell death. We also confirmed that T cells showed tumor specific antigen cytotoxicity in vitro. In adoptive transfer of CD3+ T cells into mice with pre-established tumors, we observed much higher antitumor effects of HPV-specific T cells by ELISPOT assays.
Our results show that CB derived T lymphocytes will be useful for novel immunotherapeutic candidate cells for therapy of several tumors in clinic.