Cord blood as a source of non-senescent lymphocytes for tumor immunotherapy

Abstract

While proof of concept that the immune system can be harnessed to attack cancer cells has been established, only a minority of patients are cured with immunotherapeutic regimens designed to enhance host autologous immunity. Recently acquired knowledge indicates that the low response rates associated with conventional cancer immunotherapy could be attributed, at least in part, to the processes of immunosenescence and replicative senescence, which consequently render the anti-tumor T cell clones of the aged host quantitatively insufficient and qualitatively impaired to elicit an effective anti-cancer response. Therefore, it is anticipated that the efficacy of adoptive T cell cancer immunotherapy can be dramatically improved by utilizing "young" T cells with targeted antigen specificity derived from umbilical cord blood, instead of current practice using autologous senescent T cells derived usually from aged cancer patients. Functionally competent CD8(+) T cells specific against tumor antigens (e.g. Her2/neu and MAGEA3) as well as against viral antigens have been recently generated from cord blood mononuclear cells suggesting that cord blood can be a source of "young" anti-tumor T cells for adoptive cancer immunotherapy. Moreover, cord blood can give rise to antigen non-specific effector cells including NK cells and dendritic cells. Finally, umbilical cord blood anti-tumor specific T cell clones are unlikely to have participated in tumor immunoediting, making them more efficient than host T cells in eradicating tumor cells.