{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:01:21Z","timestamp":1760954481744},"reference-count":16,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,1,16]],"date-time":"2003-01-16T00:00:00Z","timestamp":1042675200000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2003,1]]},"abstract":"<jats:p>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\u2010Gal antibody production in baboons. Xenotransplantation 2003; 10: 80\u201387. \u00a9 Blackwell Munksgaard, 2003<\/jats:p><jats:p> <jats:italic>Background:<\/jats:italic> Arsenic trioxide (As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>) 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 As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> as single therapy or in combination with an anti\u2010CD20 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\u2010\u03b1Gal1\u20103Gal antibody (anti\u2010Gal Ab) in baboons. <jats:italic>Methods:<\/jats:italic> In vitro the effect of As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> on antibody secretion (anti\u2010Gal IgM, total IgG and IgM) was measured by enzyme\u2010linked immunospot assay (ELISPOT). Its inhibition of proliferation of baboon splenocytes and the NCI\u2010H929 human plasmacytoma cell line was measured by tritiated thymidine uptake. In vivo: all baboons (n=7) had undergone splenectomy. The effects of As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> (0.18 to 0.36\u2003mg\/kg) on B\/plasma cell depletion and anti\u2010Gal Ab production were assessed in three baboons. For comparison, three baboons received either WBI (2\u2003\u00d7\u2003150\u2003cGy) or anti\u2010CD20 mAb (20\u2003mg\/kg\u2003\u00d7\u20034 doses), or both WBI and anti\u2010CD20 mAb. A final baboon received As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>\u2003+\u2003WBI (150\u2003cGy)\u2003+\u2003anti\u2010CD20\u2003mAb. Anti\u2010Gal 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. <jats:italic>Results:<\/jats:italic> In vitro: As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> (at 5\u2003\u00d7\u200310<jats:sup>\u22126<\/jats:sup>\u2003mol\/l) reduced anti\u2010Gal IgM and total IgM secretors by 76% (<jats:italic>P<\/jats:italic>=0.53) and 95% (<jats:italic>P\u2003<\/jats:italic>&lt;\u20030.001), respectively, but did not reduce total IgG secretors. As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> inhibited in a dose\u2010dependent manner the proliferation of activated splenocytes and of the NCI\u2010H929 plasmacytoma cell line; complete inhibition was achieved at a dose of 1\u2003\u00d7\u200310<jats:sup>\u22125<\/jats:sup>\u2003mol\/l. In vivo: As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> was found to be toxic at the doses given and was associated with the deaths of two of the four baboons that received it. Daily intravenous therapy with As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> alone reduced B cells (CD20+) in the blood (by 50 to 90%), BM (40%) and LN (20 to 30%), but anti\u2010Gal Ab levels were not significantly decreased. Anti\u2010CD20\u2003mAb therapy alone or WBI alone depleted B cells by 100% in the blood and BM, and 80 to 100% in the LN. The combination of anti\u2010CD20\u2003mAb\u2003+\u2003WBI led to depletion of B cells in blood, BM and LN for 3\u2003months, but reduction of anti\u2010Gal Ab remained marginal. The combination of As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>\u2003+\u2003anti\u2010CD20\u2003mAb\u2003+\u2003WBI did not reduce anti\u2010Gal Ab levels further. At autopsy in the latter baboon, B cells remained present in Peyer's patches and tonsils. <jats:italic>Conclusions:<\/jats:italic> In vitro: As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> reduced B\/plasma cell numbers and suppressed IgM secretors, but not IgG secretors. In vivo: As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> was not as effective as either anti\u2010CD20 mAb or WBI in depleting B\/plasma cells, and was largely ineffective in reducing anti\u2010Gal Ab levels. Its administration was associated with considerable toxicity. Autopsy in one baboon suggested that B cells in Peyer's patches and tonsils may be resistant to therapy and remain a source of continuing production of anti\u2010Gal Ab.<\/jats:p>","DOI":"10.1034\/j.1399-3089.2003.01136.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T23:56:43Z","timestamp":1047513403000},"page":"80-87","source":"Crossref","is-referenced-by-count":5,"title":["An exploratory investigation of the effect of arsenic trioxide on anti\u2010Gal antibody production in baboons"],"prefix":"10.1111","volume":"10","author":[{"given":"B.","family":"Gollackner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Knosalla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Basker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I. P. J.","family":"Alwayn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Harper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Salomon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Mauiyyedi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Correa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Thall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. K. C.","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,1,16]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3089.1999.00030.x"},{"key":"e_1_2_8_3_2","first-page":"559","article-title":"Identification of carbohydrate structures that bind human anti\u2010porcine antibodies: implications for discordant xenografting in humans","volume":"24","author":"GOOD AH","year":"1992","journal-title":"Transplant Proc"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199312000-00031"},{"key":"e_1_2_8_5_2","first-page":"27","article-title":"Extracorporeal immunoadsorption of anti\u2010pig antibody in pigs using \u03b1Gal oligosaccharide immunoaffinity columns","volume":"4","author":"COOPER DKC","year":"1996","journal-title":"Xeno"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199801270-00005"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3089.2001.008003157.x"},{"key":"e_1_2_8_8_2","first-page":"1041","article-title":"Arsenic trioxide and melarsoprol induce apoptosis in plasma cell lines and in plasma cells from myeloma patients","volume":"59","author":"ROUSSELOT P","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.9.3354"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3089.2000.00068.x"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1520\/JFS13302J"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8159.1999.tb06826.x"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000433-199009000-00010"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1683495"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0360-3016(95)00214-8"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.12.3457.bloodjournal85123457"},{"key":"e_1_2_8_17_2","first-page":"4824","article-title":"Systemic therapy with 3BIT, a triple combination cocktail of anti\u2010CD19, \u2010CD22, and \u2010CD38\u2010saporin immunotoxins, is curative of human B\u2010cell lymphoma in severe combined immunodeficient mice","volume":"57","author":"FLAVELL DJ","year":"1997","journal-title":"Cancer Res"}],"container-title":["Xenotransplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1034%2Fj.1399-3089.2003.01136.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1034%2Fj.1399-3089.2003.01136.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1034\/j.1399-3089.2003.01136.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T23:13:27Z","timestamp":1697238807000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1034\/j.1399-3089.2003.01136.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,1]]},"references-count":16,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2003,1]]}},"alternative-id":["10.1034\/j.1399-3089.2003.01136.x"],"URL":"https:\/\/doi.org\/10.1034\/j.1399-3089.2003.01136.x","archive":["Portico"],"relation":{},"ISSN":["0908-665X","1399-3089"],"issn-type":[{"value":"0908-665X","type":"print"},{"value":"1399-3089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,1]]}}}