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

• Hyaluronic acid-based novel powder-form combined adjuvant systems were developed.
• Powder-form adjuvant systems have an advantage in room-temperature storage stability.
• Combined adjuvant systems could significantly induce both humoral and cellular immunity.
• Hyaluronic acid-based novel adjuvant systems showed high anti-tumor immunity.

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.