Intratumoral Administration of Dendritic Cells Combined with Hyperthermia Induces Both Local and Systemic Antitumor Effect in Murine Tumor Models

Kwon, Byung Hyun; Kim, Won Taek; Ki, Young Kan; Kim, Dong Won

Abstract

PURPOSE: We examined whether intratumoral (i.t.) administration of dendritic cells (DCs) into a treated tumor could induce local and systemic antitumor effects in a mouse tumor model.
METHODS
AND MATERIALS: C57BL/6 mice were inoculated s.c. in the right and left thighs with MCA-102 fibrosarcoma cells on day 0 and on day 7, respectively. On day 7, the tumors (usually 6 mm in diameter) on the right thigh were heated by immersing the tumor-bearing leg in a circulating water bath at 43 degrees C for 30 min; thereafter, the immature DCs were i.t administered to the right thigh tumors. This immunization procedure was repeated on days 7, 14 and 21. The tumors in both the right and left thighs were measured every 7 days and the average sizes were determined by applying the following formula, tumor size=0.5 x (length+width). Cytotoxicity assay was done to determine tumor-specific cytotoxic T-lymphocyte activity.
RESULTS
Hyperthermia induced apoptosis and heat shock proteins (HSPs) in tumor occurred maximally after 6 hr. For the local treated tumor, hyperthermia (HT) alone inhibited tumor growth compared with the untreated tumors (p<0.05), and furthermore, the i.t. administered DCs combined with hyperthermia (HT+DCs) additively inhibited tumor growth compared with HT alone (p<0.05). On the distant untreated tumor, HT alone significantly inhibited tumor growth (p<0.05), and also HT+DCs potently inhibited tumor growth (p<0.001); however, compared with HT alone, the difference was not statistically significant. In addition, HT+DCs induced strong cytotoxicity of the splenocytes against tumor cells compared to DCs or HT alone.
CONCLUSION
HT+DCs induced apoptosis and increased the expression of HSPs, and so this induced a potent local and systemic antitumor response in tumor-bearing mice. This regimen may be beneficial for the treatment of human cancers.