Bispecific Antibodies and Gene Therapy

Gene therapy is the transfer of therapeutic genes, via gene transfer vectors, into patients for therapeutic purposes. Different gene therapy strategies are being pursued, including long-term gene correction of monogenetic diseases, eradication of tumor cells in cancer patients, or genetic vaccination for infectious diseases. Bispecific antibodies and gene therapy are connected in two ways. First, bispecific antibodies are tools of interest for the development of targeted gene transfer vectors. Different gene therapy strategies require different vectors, frequently replication-ablated viruses. Similar to the role of antibody engineering in antibody therapy, the engineering of gene transfer vectors has become key to the implementation of genetic therapies. Cytoablative cancer gene therapy and efficient genetic vaccination, for example, depend on vectors that are targeted to cancer cells and antigen-presenting cells, respectively, in order to avoid side effects and vector sequestration. To this end, bispecific antibodies have been engineered as adapters that link the vector to a specific molecule on the targeted cell and at the same time block the interaction with the native virus receptor. Different formats of bispecific antibodies and related molecules have been developed and succeeded in re-directing vectors to target cells in vitro and in vivo. These adapters also improved gene therapies in animal models. Second, gene transfer is a promising tool for delivery of bispecific antibodies to patients. Therefore, vectors can be injected directly into patients for antibody gene transfer, or cells isolated from patients can be genetically modified in vitro and then re-injected for in vivo antibody production. Genetic antibody delivery, compared with standard antibody injection, can be advantageous with respect to achieving persistent antibody titers or effective antibody biodistribution in patients. Initial studies have shown antibody production and therapeutic activity in animal models, setting the stage for more widespread investigations. Moreover, gene therapy can enable novel therapeutic applications for bispecific antibodies by facilitating the delivery of membrane associated or intracellular antibody formats.