Hyaluronic acid-supported combination of water insoluble immunostimulatory compounds for anti-cancer immunotherapy

Carbohydr Polym. 2017 Jan 2:155:1-10. doi: 10.1016/j.carbpol.2016.08.040. Epub 2016 Aug 16.

Abstract

A novel powder-form combination adjuvant system containing two immunostimulatory compounds was firstly developed and evaluated as a therapeutic intervention for cancer immunotherapy. With the help of hyaluronic acid (HA), water insoluble monophosphoryl lipid A (MPL), QS21 and imiquimod (R837), could be easily dispersed in aqueous solution and lyophilized as powder-form, which have an advantage in room-temperature storage stability compared with those conventional liquid formulation that requires cold storage. Two kinds of HA-based combination vaccine adjuvants (HA/MPL/QS21, HMQ and HA/MPL/R837, HMR) contributed to the increase of both humoral and cellular immunity, which is very important for efficient cancer immunotherapy. Through the challenge experiments in EG7-OVA (mouse lymphoma-expressing OVA) tumor-bearing mice model, we found out that the immunostimulatory effects of HMQ and HMR were successful in the inhibition of tumor proliferation. Taken together, both HA-based powder-form combination adjuvant systems are expected to be used as potent prophylactic and therapeutic cancer vaccine.

Keywords: Cancer immunotherapy; Cellular immunity; Hyaluronic acid; Immunostimulation; Powder-form adjuvant.

MeSH terms

  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / therapeutic use*
  • Aminoquinolines / chemistry
  • Aminoquinolines / immunology
  • Aminoquinolines / therapeutic use
  • Animals
  • Cancer Vaccines / chemistry
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Drug Carriers
  • Female
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacology*
  • Hydrogen Bonding
  • Imiquimod
  • Immunotherapy
  • Lipid A / analogs & derivatives
  • Lipid A / chemistry
  • Lipid A / immunology
  • Lipid A / therapeutic use
  • Lymphoma / immunology
  • Lymphoma / therapy*
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Saponins / chemistry
  • Saponins / immunology
  • Saponins / therapeutic use
  • Solubility

Substances

  • Adjuvants, Immunologic
  • Aminoquinolines
  • Cancer Vaccines
  • Drug Carriers
  • Lipid A
  • Saponins
  • saponin QA-21V1
  • Hyaluronic Acid
  • monophosphoryl lipid A
  • Imiquimod