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Auditing Protein Therapeutics Management by Professional APCs: Toward Prevention of Immune Responses against Therapeutic Proteins¹

Centre de Recherche des Cordeliers, Université Pierre et Marie Curie—Paris6, UMR S 872, Paris, F-75006 France; Université Paris Descartes, UMR S 872, Paris, F-75006 France; INSERM, U872, Paris, F-75006 France

Alloimmunization is a crippling concern in the management of patients undergoing administration of protein therapeutics as evidenced in replacement therapy and other treatment procedures. Several issues in the genesis and modulation of such deleterious immune responses have been studied. While authors have focused on the downstream events of the specific immune response and suggested modification of protein therapeutics to eliminate epitopes that interact with B cell receptors, T cell receptors, or MHCII molecules, the mechanisms underlying Ag interaction with APCs, a step upstream of immune effectors, have been grossly neglected. We wish to emphasize that the recent knowledge in understanding the capacities of an APC to handle an Ag and the importance of the surrounding microenvironment in this process are crucial for designing novel protein therapeutics with reduced immunogenicity.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Our work is supported by research grants from Institut National de la Santé et de la Recherche Médicale, by Centre National de la Recherche Scientifique, by Université Pierre et Marie Curie, by Agence Nationale de la Recherche Grants ANR-05-MRAR-030, ANR-07-JCJC-0100-01, ANR-07-RIB-002-02, and ANR-07-MRAR-028-01, and by Grifols (Barcelona, Spain), CSL Behring (Marburg, Germany), and LFB (Les Ulis, France). S.D. is the recipient of a fellowship from Fondation de la Recherche Médicale.

² Address correspondence and reprint requests to Dr. Sebastien Lacroix-Desmazes and Dr. Suryasarathi Dasgupta, Institut National de la Santé et de la Recherche Médicale, Unite 872, Equipe 16, Centre de Recherche des Cordeliers, 15 Rue de l’Ecole de Médecine, 75006 Paris, France. E-mail addresses: sebastien.lacroix-desmazes{at}crc.jussieu.fr and surya.dasgupta{at}gmail.com

³ Abbreviations used in this paper: DC, dendritic cell; PEGylation, derivatization of A protein with polyethylene glycol; Treg, regulatory T cell.