Combined Immunotherapy Against Cancer: Limited Efficacy of Transcutaneous Immunization and Low-dose Cyclophosphamide

Julia Umansky, Michael Weber, Hansjörg Schild, Markus P. Radsak, Pamela Stein
2015 Cancer and Oncology Research  
Transcutaneous immunization (TCI) is a novel vaccination strategy with a promising potential for combating tumors or persistent infectious diseases. However, imiquimod-based TCI, we have previously developed, shows only limited effectiveness in terms of tumor protection, partly due to suppression by regulatory T (Treg) cells. To improve the vaccination potency we combined TCI with the cytotoxic drug cyclophosphamide (Cy) that is used for the treatment of tumors and described to mediate
more » ... to mediate inactivation of Treg cells at low doses. Cy only slightly reduced Treg cell numbers in a concentration dependent manner under the chosen conditions, but also enhanced DC activation. Therefore, we used Cy-TCI in a therapeutic tumor assay where E.G7 lymphomas were subcutaneously transplanted and allowed to grow until palpable before the treatments started. Interestingly, the rates of tumor protection in TCI or Cy-TCI treated groups were identical. Towards the underlying mechanisms of the failure of Cy-TCI to provide enhanced tumor protection, we observed increased numbers of monocytic and granulocytic immature myeloid cells after Cy-TCI, partly suppressing TCI-induced immune responses. Taken together, we suggest that Cy-TCI induces inhibitory mechanisms counterregulating TCI enhancing effects, therefore suppressing vaccination-induced immune responses.
doi:10.13189/cor.2015.030101 fatcat:rqvzqzuvxjenxit7y3zw4k4yxi