The pretargeted therapy involved TF10, a humanized bispecific antibody that binds to the same pancreatic cancer mucin as the antibody PAM4. TF10 was created by the company’s protein engineering platform technology known as Dock-and-Lock, developed with scientists of IBC Pharmaceuticals, a majority-owned subsidiary of Immunomedics.
Mice bearing human pancreatic cancer cells were first given the DNL-derived antibody. After 16 hours, yttrium-90 (Y-90) labeled histamine-succinyl-glycine peptide was injected, and then became bound by the bispecific antibody on the tumor, thus achieving selective targeting of the therapeutic.
This pretargeted system arrested the growth of established tumors without appreciable hematologic toxicity, and extended median survival time (MST) to 4.9 weeks compared to 3.7 weeks from the untreated group. MST improved to 18.9 weeks when the pretargeted therapy was administered in three fractions, one fraction every four weeks in combination with gemcitabine. Gemcitabine alone had no significant effect on inhibiting tumor growth, extending MST to only 4.4 weeks.
Cynthia Sullivan, president and CEO of Immunomedics, said: “These results suggested that fractionated radioimmunotherapy potentially can be applied to pretargeting.”