Cytokine-induced killer (CIK) cells are often compromised by their lack of tumor targeting and long-term activity against solid tumors. Herein, we report an interferon-α (IFN-α) encapsulated hydrogel and low dose irradiation (LDI) as CIK sensitizers for gastric cancer therapy.
IFN-α2b was incorporated in an ultraviolet-reactive, rapidly cross-linkable hydroxypropyl cellulose (HPC) hydrogel. The physicochemical and drug release profiles were characterized. The CIK accumulation upon LDI at tumor site was invesigated. The antitumor efficacy of combining CIK cells, IFN-α2b loaded hydrogels and LDI was explored in a gastric cancer xenografted mouse model.
The HPC hydrogels exhibited a porous structure, consisting of open pore channels and an interconnected framework. The bioactivity of IFN-α2b was well-maintained in the hydrogels with constant release profile. CIK cells accumulated into tumors irradiated by a 5 Gy dose, indicating local LDI provided the possibility of recruitment of immune cells to the tumor site. The tumor growth inhibition on gastric cancer bearing mice was 59% of Gel-IFN + CIK + LDI group, which was higher than the IFN-a2b alone (11.7%, P < 0.01) and IFN-a2b + CIK + LDI (43.3%, P < 0.01). The tumor weight inhibition was 52%, while they were 4.7% and 33.0% in IFN-a2b alone and IFN-a2b + CIK + LDI, respectively (P < 0.01).
This innovative combination of CIK cells, IFN-α2b loaded hydrogels with cancer radiation serve as a potent strategy for gastric cancer treatment.
Clinical trial identification
Legal entity responsible for the study
Nanjing Drum Tower Hospital.
Has not received any funding.
All authors have declared no conflicts of interest.