Host immune response to anti-cancer camptothecin conjugated cyclodextrin-based polymers
| Autor: | Mark E. Davis, Chun A. Changou, Yi Fan Chen, Yen Hsin Wang, Cing Syuan Lei, Yun Yen |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Endocrinology Diabetes and Metabolism T cell Clinical Biochemistry Central nervous system lcsh:Medicine Antineoplastic Agents Review Immune responses Adaptive Immunity Pharmacology Efficacy Mice 03 medical and health sciences Nanoparticle 0302 clinical medicine Immune system Animals Medicine Pharmacology (medical) Cellulose Adverse effect Molecular Biology Cyclodextrins business.industry lcsh:R Biochemistry (medical) Cancer Cell Biology General Medicine medicine.disease Immunity Innate Specific Pathogen-Free Organisms Brain tumor 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer cell Nanoparticles Camptothecin business medicine.drug |
| Zdroj: | Journal of Biomedical Science, Vol 26, Iss 1, Pp 1-12 (2019) Journal of Biomedical Science |
| ISSN: | 1423-0127 |
| DOI: | 10.1186/s12929-019-0583-0 |
| Popis: | Introduction Efficacy and safety are critical concerns when designing drug carriers. Nanoparticles are a particular type of carrier that has gained recent attention in cancer therapeutics. Methods In this study, we assess the safety profile of IT-101, a nanoparticle formed by self-assembly of camptothecin (CPT) conjugated cyclodextrin-based polymers. IT-101 delivers CPT to target cancer cells in animal models of numerous human cancers and in humans. Previous data from preclinical and clinical trials indicate that IT-101 has no notable immunological side effects. However, there have been no published studies focused on evaluating the effects of IT-101 on host immune systems. Results In this work, we demonstrate that IT-101 diminished initial host immune response following first injection of the nanopharmaceutical and induced NK cell activation and T cell proliferation upon further IT-101 exposure. Additionally, IT-101 could attenuate tumor growth more efficiently than CPT treatment only. Conclusions Drugs administration in whole-body circulation may lead to poorly bioavailable in central nervous system and often has toxic effects on peripheral tissues. Conjugated with cyclodextrin-based polymers not only reduce adverse effects but also modulate the immune responses to elevate drug efficacy. These immune responses may potentially facilitate actions of immune blockage, such as PD1/PDL1 in cancer treatment. |
| Databáze: | OpenAIRE |
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