In Vivo Secretion of Bispecific Antibodies Recruiting Lymphocytic Effector Cells

Abstract

Engineered Fc-lacking bispecific antibodies have shown an exceptionally high potency for recruiting lymphocyte effector cells and enhancing antitumor activity, which is under evaluation in several clinical trials. However, current treatment regimens raise some issues that should be considered, such as the high cost of clinical-grade bispecific antibodies and the achievement of sustained therapeutic plasma levels. The use of gene transfer methods may circumvent problems related to large-scale production and purification, and result in sustained therapeutic plasma concentrations of the Fc-lacking bispecific antibodies. In fact, terminally differentiated cells and non-terminally differentiated cells can be genetically modified to secrete functionally active bispecific antibodies exerting clear anti-tumor effects. This review highlights the relevance of different promising strategies for in vivo delivery of therapeutic bispecific antibodies

In Situ Liver Expression of HBsAg/CD3-Bispecific Antibodies for HBV Immunotherapy

“… 15 These hurdles could be overcome through in situ expression of bispecific Abs from DNA or RNA templates in patient tissues, but there have been few reports on such strategies. 16 , 17 , 18 The liver absorbs major fractions of gene therapy vectors, nanoparticles, or liposomes, allowing gene constructs to be delivered more readily than in any other organ. Expression of bispecific Abs in the liver should have several advantages compared to the passive infusion of recombinant proteins for treating HBV.…”