Anti-non-Gal-specific combination treatment with an anti-idiotypic Ab and an inhibitory small molecule mitigates the xenoantibody response
John M Stewart, Alice F Tarantal, Yan Chen, Nancy C Appleby, Tania I Fuentes, C Chang I Lee, Evelyn J Salvaris, Anthony JF d'Apice, Peter J Cowan, Mary Kearns-Jonker
XENOTRANSPLANTATION | WILEY | Published : 2014
BACKGROUND: B-cell depletion significantly extends survival of α-1,3-galactosyltranferase knockout (GTKO) porcine organs in pig-to-primate models. Our previous work demonstrated that the anti-non-Gal xenoantibody response is structurally restricted. Selective inhibition of xenoantigen/xenoantibody interactions could prolong xenograft survival while preserving B-cell-mediated immune surveillance. METHODS: The anti-idiotypic antibody, B4N190, was selected from a synthetic human phage display library after enrichment against a recombinant anti-non-Gal xenoantibody followed by functional testing in vitro. The inhibitory small molecule, JMS022, was selected from the NCI diversity set III using vi..View full abstract
Awarded by NIH
Awarded by Primate Center base operating grant
Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
ALPHA;-1,3-galactosyltranferase knockout endothelial cells (PEGKO42) were kindly provided by Dr. David Sachs, Massachusetts General Hospital. We also thank Hector Almanzar, Billy Watson, and Michele Martinez for technical assistance. This study was supported by NIH grant no. RO1AI052079 (MKJ) and the Primate Center base operating grant no. OD011107 (AFT).