Metronomic chemotherapy enhances antitumor effects of cancer vaccine by depleting regulatory T lymphocytes and inhibiting tumor angiogenesis
Journal
Molecular Therapy
Journal Volume
1233
Journal Issue
1243
Pages
1233-1243
Date Issued
2010
Author(s)
Ho C.-M.
Chang M.-C.
Syu M.-H.
Abstract
Although cancer vaccines are emerging as innovative methods for cancer treatment, these alone have limited potential for treating measurable tumor burden. Thus, the importance of identifying anticancer strategies with greater potency is necessary. The chimeric DNA vaccine CTGF/E7 (connective tissue growth factor linked to the tumor antigen human papillomavirus 16 E7) generates potent E7-specific immunity and antitumor effects. We tested immune-modulating doses of chemotherapy in combination with the CTGF/E7 DNA vaccine to treat existing tumors in mice. Metronomic low doses of paclitaxel, not the maximal tolerable dose, are synergistic with the antigen-specific DNA vaccine. Paclitaxel, given in metronomic sequence with the CTGF/E7 DNA vaccine enhanced the vaccine's potential to delay tumor growth and decreased metastatic tumors in vivo better than the CTGF/E7 DNA vaccine alone. The two possible mechanisms of metronomic paclitaxel chemotherapy are the depletion of regulatory T cells and the inhibition of tumor angiogenesis rather than direct cancer cell cytolytic effects. Results indicate that combination treatment of metronomic chemotherapy and antigen-specific DNA vaccine can induce more potent antigen-specific immune responses and antitumor effects. This provides an immunologic basis for further testing in cancer patients. ? The American Society of Gene & Cell Therapy.
SDGs
Other Subjects
connective tissue growth factor linked to the tumor antigen human papillomavirus 16 E7; DNA vaccine; paclitaxel; unclassified drug; antineoplastic agent; cancer vaccine; paclitaxel; animal cell; animal experiment; animal model; antiangiogenic activity; antineoplastic activity; article; cancer inhibition; drug dose comparison; drug mechanism; drug potentiation; immunomodulation; low drug dose; lung tumor; metastasis; mouse; nonhuman; T cell depletion; tumor vascularization; animal; human; immunology; lymphocyte depletion; Neoplasms; neovascularization (pathology); regulatory T lymphocyte; vascularization; Animals; Antineoplastic Agents; Cancer Vaccines; Humans; Lymphocyte Depletion; Mice; Neoplasms; Neovascularization, Pathologic; Paclitaxel; T-Lymphocytes, Regulatory; Human papillomavirus - 16; Human papillomavirus type 16; Mus; Animals; Antineoplastic Agents; Cancer Vaccines; Humans; Lymphocyte Depletion; Mice; Neoplasms; Neovascularization, Pathologic; Paclitaxel; T-Lymphocytes, Regulatory
Type
journal article