化疗可与过继性免疫治疗协同抑制髓母细胞瘤生长

With the commercial medulloblastoma cell line, Daoy, we explored the concentrations of combinations of Gemcitabine with rapamycin needed to induce cytotoxicity. Next, we used flow cytometry to assess the cytotoxicity of chemotherapy-treated Daoy cells with the addition of anti-tumor T-cells, generated from naive T-cells stimulated in the presence of Daoy lysate-pulsed dendritic cells. Then, we examined the efficacy of chemotherapy alone versus chemotherapy plus immunotherapy in tumor growth inhibition of subcutaneous medulloblastoma xenografts.

Rapamycin alone at <1,000 nM had moderate activity against Daoy cells in vitro and IC 50 was >1,000 nM. Gemcitabine had a 3-day IC 50 alone of 10 nM but in combination with 100 nM rapamycin, it decreased to 1 nM, suggesting increased cytotoxicity with combined therapy. Stimulated T-cells mediated in-vitro cytotoxicity, although background cytotoxicity of unstimulated "naïve" T-cells was also significant. Finally, established subcutaneous Daoy cell xenografts in SCID mice were treated with chemotherapy alone or chemotherapy plus adoptive immunotherapy (stimulated and non-stimulated). Gemcitabine and rapamycin alone significantly slowed tumor growth, but the addition of immunotherapy further augmented inhibition.

Combining immunotherapy and chemo-biologic therapy inhibit medulloblastoma cell and xenograft growth, and may offer an effective treatment for patients with medulloblastoma.