Abstract

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.

Original languageEnglish
Number of pages1
JournalJournal of Biomedical Science
Volume26
Issue number1
DOIs
Publication statusPublished - Oct 23 2019

Fingerprint

Camptothecin
Cyclodextrins
Polymers
Neoplasms
Nanoparticles
Safety
Drug Carriers
Oncology
T-cells
Immune system
Poisons
Cell proliferation
Neurology
IT-101
cyclodextrin polymer
Natural Killer Cells
Pharmaceutical Preparations
Self assembly
Tumors
Immune System

Keywords

  • Brain tumor
  • Camptothecin
  • Immune responses
  • Nanoparticle

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

Cite this

Host immune response to anti-cancer camptothecin conjugated cyclodextrin-based polymers. / Chen, Yi Fan; Wang, Yen Hsin; Lei, Cing Syuan; Changou, Chun A.; Davis, Mark E.; Yen, Yun.

In: Journal of Biomedical Science, Vol. 26, No. 1, 23.10.2019.

Research output: Contribution to journalReview article

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AU - Chen, Yi Fan

AU - Wang, Yen Hsin

AU - Lei, Cing Syuan

AU - Changou, Chun A.

AU - Davis, Mark E.

AU - Yen, Yun

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N2 - 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.

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