1. Phototherapy using immunologically modified carbon nanotubes to potentiate checkpoint blockade for metastatic breast cancer.
- Author
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Li, Yong, Li, Xiaosong, Doughty, Austin, West, Connor, Wang, Lu, Zhou, Feifan, Nordquist, Robert E., and Chen, Wei R.
- Subjects
SINGLE walled carbon nanotubes ,METASTATIC breast cancer ,CARBON nanotubes ,TUMOR antigens ,PHOTOTHERAPY ,THERAPEUTICS - Abstract
Metastasis is the major cause of cancer-death. Checkpoint inhibition shows great promise as an immunotherapeutic treatment for cancer patients. However, most currently available checkpoint inhibitors have low response rates. To augment the antitumor efficacy of checkpoint inhibitors, such as CTLA-4 antibodies, a single-walled carbon nanotube (SWNT) modified by a novel immunoadjuvant, glycated chitosan (GC), was used for the treatment of metastatic mammary tumors in mice. We treated the primary tumors by intratumoral administration of SWNT-GC, followed with irradiation with a 1064-nm laser to achieve local ablation through photothermal therapy (PTT). The treatment induced a systemic antitumor immunity which inhibited lung metastasis and prolonged the animal survival time of treated. Combining SWNT-GC-laser treatment with anti-CTLA-4 produced synergistic immunomodulatory effects and further extended the survival time of the treated mice. The results showed that the special combination, PTT + SWNT-GC + anti-CTLA, could effectively suppress primary tumors and inhibit metastases, providing a new treatment strategy for metastatic cancers. Laser immunotherapy is an effective treatment modality for metastatic cancers. Single-walled carbon nanotubes (SWNTs), functionalized with an immunoadjuvant, glycated chitosan (GC), can increase the specificity and efficacy of the treatment, upon laser irradiation. Moreover, the treatment can potentiate the suppression of regulatory T cells checkpoint inhibitors such as anti-CTLA-4 antibodies. The combination treatment of laser-SWNT-GC enhances tumor antigen uptake and presentation, hence activating T cells to destroy residual tumor cells at the treatment sites as well as metastatic tumor cells at distant sites. Unlabelled Image [ABSTRACT FROM AUTHOR]
- Published
- 2019
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