Human umbilical cord blood mononuclear cells (UCBC) are rich source of antitumor cytotoxic effector cells. In this report we describe the generation of antigen non-specific and specific cytotoxic cells from UCBC against human breast cancer cells. Methods: For the non-specific effector cells, mononuclear cells from UCBC were activated with IL-2, IL-15, GM-CSF, G-CSF and M-CSF either alone or in combination in vitro. For the antigen specific cytotoxic T lymphocyte generation, dendritic cells were generated from UCBC using DC specific media and were primed with Her2/neu specific peptide (KIFGSLAFL). Such antigen primed dendritic cells were used to augment the cytotoxicity of CD* positive CTLs from UCBC. Following activation with cytokines or antigen primed dendritic cells, the cytotoxicity of these effector cells were tested against MDA-231, MDA-453 and SKBr3 human breast cancer cells. Results: 1) Antigen Non-Specific Effectors: Cord blood cells activated with IL-15 in combination with GM-CSF showed significantly higher cytotoxicity against breast cancer cells compared to IL-2 alone or other cytokine combinations (P<0.01). The cytokine combination significantly increased CD8+ and CD56+ cells (P<0.01) and correlated with increase in cytotoxicity (r=0.976). RT-PCR analysis of the cytokine activated UCBC showed an increase in Th1 type cytokines gene expression. 2) Antigen-Specific Effectors: Dendritic cell primed Her2/neu specific CTLs showed a significant cytotoxicity against Her2/neu high-expressing human MDA-453 and SKBr3 but not against Her2/neu low-expressing MDA-231 breast cancer cells. Conclusion: These results indicate that both antigen non-specific and antigen specific cytotoxic effector cells can be generated from cord blood against breast cancer. These studies lay a foundation for development of concurrent cord blood derived cellular therapy for breast cancer to eliminate both antigen negative and antigen positive breast cancer cells in patients.
|Original language||English (US)|
|Number of pages||1|
|Journal||Breast Cancer Research and Treatment|
|State||Published - 2001|
ASJC Scopus subject areas
- Cancer Research