CpG A ODN can activate tumorspecific lymphocytes in the orthotopic VX2 hepatoma in rabbits

Solid malignant hepatic lesion such as metastases or primary liver cancer are still an unsolved burden of gastrointestinal oncology. ODN CpG have shown a specific reactivity to certain TLR receptors on dendritic cells. Recently it was shown, that CpG A is a potent drug recruiting especially T memory cells by activation of TLR 8 and 9.

The aim of this study was to show if ODN CpG A is effective in the solid VX2 hepatoma model in rabbits.

Material and Methods:

12 rabbits suffering from a VX2 hepatoma were treated with ODN CpG A for 120 and were sacrificed thereafter.

Blood was sampled into citrate buffer before implantation and every 2 weeks thereafter.

PBMC were isolated and were tested for specific activation by tritium incorporation assay. Autologous tumor tissue lysate served as testantigen, autologous liver tissue lysate as negative control and the mitogen phytohemagglutenine (PHA) as positive control. The stimulation index (SI) was calculated by the ratio of PBMC stimulated with tumor tissue vs. liver tissue and compared to baseline.

Results:

Mean survival time was 79,4d (±12,3) for treated animals and 41,3d (±9,2) for untreated controls.

All controls had primary liver tumors and secondary as well. 2 animals of the treated group showed no malignant tissue at the end of observation, 3 had only primary liver tumors and 1 animal showed primary tumors and metastases as well.

Before tumor implantation and 2 weeks after implantation both groups showed no significant tumor specific activation of lymphocytes (SI=1,4;±0,67). This was maintained up to week 8 after implantation. In the treated group the SI rose up to 32,1 (±6,98) while the controls showed no significant T cell activation.

Discussion:

CpG A is a potent stimulator of tumor specific immune response in solid malignancy CpG A seems to overcome immune tolerance towards malignant tissue This CpG ODN should be tested in further multimodal clinical trials.