Efficacy of combined administration of chemoimmunotherapy with bone marrow cells or granulocyte-colony stimulating factor-mobilized stem cells on expansion of myeloid and stem cells

Soha Gomaa Ramadan Abdel Salam, Mohamed Labib Salem, Mohamed Nassef, Said Hammad Abdu, Rania El-Adl

Clinical Cancer Investigation Journal 2017 6(1):73-80

Background: Integrating immunotherapy and chemotherapy is most likely to be the basis for new optimism in targeting cancer therapies to form local tumor microenvironment and attack tumors early in their development. This regimen has some potential risks such as myelo- and immunosuppression and chemo-resistant tumor cells. Aim: The present study aimed to investigate the combination of chemotherapy, immunotherapy, and the prospective of mobilized stem cells for optimization and modulation of the immune system to overcome immunosuppression and kill distant cancer cells. Materials and Methods: Ehrlich ascetic carcinoma (EAC) cell line-bearing mice treated with cyclophosphamide (CTX) followed by adoptively transferred with in vitro-activated T-cells either harvested from naïve or EAC-bearing host with or without unfractionated bone marrow (BM) cells or granulocyte-colony stimulating factor-mobilized hematopoietic stem cells (HSCs) 1-day post-CTX treatment. All mice were vaccinated with EAC lysate and Hiltonol. Results: Cotransfer of activated T-cells obtained from EAC-bearing mice with HSC-progenitors induced the highest antitumor effect through increasing the percentage of apoptosis and decreasing DNA replication in S phase of EAC cells. Besides, marked an increase in the percentage of myeloid cells in spleen and stem cell populations in BM cells. Interestingly, Adoptive T-cell transfer (ACT) derived from EAC-bearing host with or without BM cells induced mobilization of stem cells from BM to circulation increasing their expansion. Conclusion: Combination of chemotherapy with ACT plus vaccination may constitute a potent antitumor therapy that provides more efficacious antitumor responses when it is combined with BM cells fostering more effective antitumor immunotherapy strategies.

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