Host immune response to anti-cancer camptothecin conjugated cyclodextrin-based polymers

J Biomed Sci. 2019 Oct 23;26(1):85. doi: 10.1186/s12929-019-0583-0.


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.

Keywords: Brain tumor; Camptothecin; Immune responses; Nanoparticle.

MeSH terms

  • Adaptive Immunity / drug effects*
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Camptothecin / administration & dosage*
  • Cellulose / administration & dosage*
  • Cyclodextrins / administration & dosage*
  • Immunity, Innate / drug effects*
  • Mice
  • Nanoparticles / administration & dosage*
  • Specific Pathogen-Free Organisms


  • Antineoplastic Agents
  • Cyclodextrins
  • IT-101
  • cyclodextrin polymer
  • Cellulose
  • Camptothecin