An exploratory investigation of the effect of arsenic trioxide on anti-Gal antibody production in baboons

Gollackner B, Ryan D, Knosalla C, Basker M, Alwayn IPJ, Harper D, Salomon G, Mauiyyedi S, Correa L, Thall A, Cooper DKC. An exploratory investigation of the effect of arsenic trioxide on anti‐Gal antibody production in baboons. Xenotransplantation 2003; 10: 80–87. © Blackwell Munksgaard, 2003 Background: Arsenic trioxide (As2O3) is an anticancer drug that has been reported to induce apoptosis and inhibit differentiation in human plasmacytoma and normal plasma/B cells without significant myelosuppression. We assessed the ability of As2O3 as single therapy or in combination with an anti‐CD20 monoclonal antibody (mAb) and whole body irradiation (WBI) to deplete B and plasma cells, both in vitro and in vivo, and to reduce the level of anti‐αGal1‐3Gal antibody (anti‐Gal Ab) in baboons. Methods: In vitro the effect of As2O3 on antibody secretion (anti‐Gal IgM, total IgG and IgM) was measured by enzyme‐linked immunospot assay (ELISPOT). Its inhibition of proliferation of baboon splenocytes and the NCI‐H929 human plasmacytoma cell line was measured by tritiated thymidine uptake. In vivo: all baboons (n=7) had undergone splenectomy. The effects of As2O3 (0.18 to 0.36 mg/kg) on B/plasma cell depletion and anti‐Gal Ab production were assessed in three baboons. For comparison, three baboons received either WBI (2 × 150 cGy) or anti‐CD20 mAb (20 mg/kg × 4 doses), or both WBI and anti‐CD20 mAb. A final baboon received As2O3 + WBI (150 cGy) + anti‐CD20 mAb. Anti‐Gal Ab levels were measured daily by ELISA. Depletion of B cells from blood and bone marrow (BM) was monitored by flow cytometry and by histology of lymph nodes (LN). Autopsy was performed in three baboons. Results: In vitro: As2O3 (at 5 × 10−6 mol/l) reduced anti‐Gal IgM and total IgM secretors by 76% (P=0.53) and 95% (P