Immunomedics constructs anti-lymphoma antibodies

Designated as TF3 and TF5, the new bispecific constructs were created using the Dock and Lock (DNL) method recently published in the Proceedings of the National Academy of Sciences. Both constructs are fully humanized, comprised of Immunomedics’ humanized anti-CD20 (hA20) antibody and humanized anti-CD22 antibody, epratuzumab.

TF3 is made up of two anti-CD20 antibody fragments linked to one anti-CD22 antibody fragment, whereas TF5 was constructed by fusing two anti-CD22 antibody fragments to one anti-CD20 fragment.

TF3 and TF5 were shown to be stable in both human and mouse sera. Both bispecific antibodies inhibited the growth of human lymphoma cell lines in vitro. Under the same experimental conditions, TF3 showed a 1,000-fold higher potency as compared to the parent antibody, hA20, which also reflects a higher cytotoxicity over rituximab, since hA20 has been shown to be similar in activity to rituximab.

The anti-proliferative activity of TF3 and TF5 is attributed to the ability of the two bispecific antibodies to cross-link CD20 and CD22. These encouraging studies are now being expanded to compare these bispecific antibodies to epratuzumab, hA20, and rituximab in animal models of human lymphoma, with the intention of bringing the best construct into clinical testing.