Fractionated pretargeted radioimmunotherapy (PT-RAIT) of pancreatic cancer xenografts

Objectives Pretargeting is a promising procedure for improving RAIT with less hematologic toxicity. We evaluated fractionated therapy with ⁹⁰Y-DOTA-di-HSG peptide (⁹⁰Y-IMP-288) and TF10, a humanized recombinant bispecific antibody with 2 Fabs that bind a pancreatic cancer mucin antigen identified by the antibody PAM4, and 1 Fab binding to the hapten HSG (histamine-succinyl-glycine).

Methods Studies were performed in nude mice bearing s.c. CaPan1 human pancreatic cancer xenografts with initial tumor volumes of, 0.32-0.54cm³. For therapy, TF10-pretargeted ⁹⁰Y-IMP-288 was given once [A] (0.6mCi on wk 0) or fractionated [B] (0.3 mCi on wks 0 and 1), [C] (0.2 mCi on wks 0, 1 and 2) or [D] (0.2 mCi on wks 0, 1 and 4).

Results Tumor regression (>90%) was observed in the majority of mice, 9/10, 10/10, 9/10 and 8/10 in groups [A], [B], [C] and [D], respectively. In group [A], maximum tumor regression in 50 % of the mice was reached at 3.7 wks, compared to 6.1, 8.1 and 7.1 wks in [B], [C] and [D], respectively. Some tumors showed regrowth. At week 14, the best therapeutic response was observed in the fractionated group (2x0.3 mCi), with 6/10 mice having no tumors (NT) compared to 3/10 in the 3x0.2 mCi groups and 1/10 in the 1x 0.6mCi group. No major body weight loss was observed in any of the treatment groups.

Conclusions Fractionated PT-RAIT provides another alternative for treatment of pancreatic cancer with minimum toxicity.

Research Support Supported in part by grant NCI CA 109474