Potential therapeutic utility of hybridized IgG4 antibodies

Abstract

Targeted cancer immunotherapy requires identifying and targeting an antigen preferentially present in the individual patient’s tumor as compared to that patient’s normal tissues. Manufacturing a fully targeted antibody can be time consuming and expensive, limiting the use of targeted immunotherapy as personalized cancer medicine.An IgG4 molecule, whether in vitro or in vivo, tends to exchange a half of itself with another IgG4 molecule. This biological characteristic creates IgG4 hybrids with bifunctional specificity. It is hypothesized that this IgG4 characteristic can be exploited to therapeutic advantage in creating highly targeted immunotherapy.An hypothesized strategy to more easily achieve personalized immunotherapy is to create a generic non-targeted immunologic IgG4 agent, but then to use the patient’s own ability to create the targeting via their endogenous IgG4 antitumor antibodies, recombining these two in the form of a bifunctionalIgG4 antibody. The manufactured half would carry the therapeutic moiety (such as a radioactive agent or a toxin) and the endogenous half would afford the personalized antitumor specificity.