Monoclonal antibody 14C5: Potential use in radioimmunotherapy of pancreatic cancer

Objectives The therapeutic efficiency of the monoclonal antibody (mAb) 14C5 was investigated in a human pancreatic tumour model. Radioimmunotherapy (RAIT) with ¹³¹I-mAb 14C5 and RAIT in combination with gemcitabine were performed.

Methods Mice were grafted with the human pancreatic tumour cell line Capan-1 and different treatment regiments were assessed: ¹³¹I-mAb 14C5 (3.7-7.4-22.2 MBq/mouse) and ¹³¹I-mAb 14C5 in combination with gemcitabine (5x2 mg gemcitabine + 3.7-7.4 MBq/mouse). 7 mice were allocated to each group and control groups were included (PBS, ¹³¹I-nonspecific MAB002 and gemcitabine). Tumour measurement, weighing and blood analysis (rbc-, wbc-, platelets-count) were performed weekly.

Results From day 17, a significant slower tumour growth (p<0.05) was seen in the highest ¹³¹I-14C5 treatment groups, with a 1.5- and 2.0-fold smaller tumour size at day 44 (for 7.4 and 22.2 MBq respectively compared to the PBS control group). At the dose level of 7.4 MBq, ¹³¹I-14C5 combined with gemcitabine provided significantly greater anti-tumour activity than did the gemcitabine alone (p<0.002) or ¹³¹I-nonspecific MAB002 (p<0.02). The combined modality of gemcitabine and ¹³¹I-RAIT was well tolerated by the mice, with a recovery in body weight within 4 weeks after start of the treatment. Although the effects on rbc, wbc and platelets were similar in both ¹³¹I-mAb 14C5 and ¹³¹I-MAB002 treated mice, mice receiving gemcitabine combined with ¹³¹I-MAB002 had a greater mean loss and recovered more slowly.

Conclusions RAIT with mAb14C5 is a promising approach for the treatment of pancreatic cancer.