Cyclophosphamide, doxorubicin, and paclitaxel enhance the antitumor immune response of granulocyte/macrophage-colony stimulating factor-secreting whole-cell vaccines in HER-2/neu tolerized mice
| Autor: | J P, Machiels, R T, Reilly, L A, Emens, A M, Ercolini, R Y, Lei, D, Weintraub, F I, Okoye, E M, Jaffee |
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| Přispěvatelé: | UCL - MD/MINT - Département de médecine interne, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Centre du cancer |
| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Paclitaxel
T-Lymphocytes Epitopes T-Lymphocyte Granulocyte-Macrophage Colony-Stimulating Factor Mammary Neoplasms Experimental Drug Synergism Mice Transgenic 3T3 Cells Genes erbB-2 Th1 Cells Lymphocyte Activation Cancer Vaccines Combined Modality Therapy Drug Administration Schedule Rats Mice Doxorubicin Antineoplastic Combined Chemotherapy Protocols Immune Tolerance Animals Humans Female Cyclophosphamide |
| Zdroj: | Cancer Research, Vol. 61, no.9, p. 3689-3697 (2001) |
| Popis: | Tumor-specific immune tolerance limits the effectiveness of cancer vaccines. In addition, tumor vaccines alone have a limited potential for the treatment of measurable tumor burdens. This highlights the importance of identifying more potent cancer vaccine strategies for clinical testing. We tested immune-modulating doses of chemotherapy in combination with a granulocyte/macrophage-colony stimulating factor (GM-CSF)-secreting, HER-2/neu (neu)-expressing whole-cell vaccine as a means to treat existing mammary tumors in antigen-specific tolerized neu transgenic mice. Earlier studies have shown that neu transgenic mice exhibit immune tolerance to the neu-expressing tumors similar to what is observed in patients with cancer. We found that cyclophosphamide, paclitaxel, and doxorubicin, when given in a defined sequence with a GM-CSF-secreting, neu-expressing whole-cell vaccine, enhanced the vaccine's potential to delay tumor growth in neu transgenic mice. In addition, we showed that these drugs mediate their effects by enhancing the efficacy of the vaccine rather than via a direct cytolytic effect on cancer cells. Furthermore, paclitaxel and cyclophosphamide appear to amplify the T helper 1 neu-specific T-cell response. These findings suggest that the combined treatment with immune-modulating doses of chemotherapy and the GM-CSF-secreting neu vaccine can overcome immune tolerance and induce an antigen-specific antitumor immune response. These data provide the immunological rationale for testing immune-modulating doses of chemotherapy in combination with tumor vaccines in patients with cancer. |
| Databáze: | OpenAIRE |
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