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Blood, 1 May 2004, Vol. 103, No. 9, pp. 3303-3304.
Prepublished online as a Blood First Edition Paper on January 22, 2004; DOI 10.1182/blood-2003-11-3845.
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GENE THERAPY
Brief report
Autoimmune anemia in macaques following erythropoietin gene therapy
Pierre Chenuaud,
Thibaut Larcher,
Joseph E. Rabinowitz,
Nathalie Provost,
Yan Cherel,
Nicole Casadevall,
Richard J. Samulski, and
Philippe Moullier
From the Institut National de la Santé et de la Recherche Médicale (INSERM), Nantes, France; University of North Carolina (UNC) Gene Therapy Center, UNC, Chapel Hill, NC; Ecole Nationale Vetérinaire, Nantes, France; and Service d'Hématologie Biologique, Paris, France.
We delivered the homologous erythropoietin (Epo) cDNA driven from a doxycycline-regulated promoter via recombinant adeno-associated virus in skeletal muscle of 9 cynomolgus macaques. Upon induction, rapid supraphysiologic levels of Epo were obtained. Unexpectedly, some individuals developed a profound anemia that correlated with the appearance of neutralizing antibodies against the endogenous Epo. Both the endogenous erythropoietin and vector sequences were identical. This is the first example of the inadvertent development of an autoimmune disease in primates as a result of gene transfer of a gene expressing a self-antigen. It raises some concerns when a therapeutic protein is produced at high levels from an ectopic site. (Blood. 2004;103:3303-3304)
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