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Abstract
Therapeutic monoclonal antibodies have revolutionized the treatment of cancer and other diseases. However, several limitations of antibody-based treatments, such as the cost of therapy and the achievement of sustained plasma levels, should be still addressed for their widespread use as therapeutics. The use of cell and gene transfer methods offers additional benefits by producing a continuous release of the antibody with syngenic glycosylation patterns, which makes the antibody potentially less immunogenic. In vivo secretion of therapeutic antibodies by viral vector delivery or ex vivo gene modified long-lived autologous or allogeneic human mesenchymal stem cells may advantageously replace repeated injection of clinical-grade antibodies. Gene-modified autologous mesenchymal stem cells can be delivered subcutaneously embedded in a non-immunogenic synthetic extracellular matrix-based scaffold that guarantees the survival of the cell inoculum. The scaffold would keep cells at the implantation site, with the therapeutic protein acting at distance (immunotherapeutic organoid), and could be retrieved once the therapeutic effect is fulfilled. In the present review we highlight the practical importance of living cell factories for in vivo secretion of recombinant antibodies.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
This study was supported by grants from the Ministerio de Ciencia e Innovación (BIO2011-22738 and PSE-01000-2009-11), the Comunidad de Madrid (S2010/BMD-2312), and the European Union (SUDOE-FEDER. IMMUNONET-SOE1/P1/E014) to L.A-V; and from the Fondo de Investigación Sanitaria/ Instituto de Salud Carlos III (PI08/90856 and PS09/00227) and Fundación Investigación Biomédica Hospital Puerta de Hierro to L.S.