BACKGROUND: Antithymocyte globulins (ATGs) are used to prevent and treat allograft rejection and graft versus host disease. They are purified IgG fractions derived from rabbits immunized with the Jurkat T-cell line (ATG-Fresenius) or thymus cells (Thymoglobulin). Differences not only in the amounts of leukocyte reactive antibodies but also in the antigens targeted by ATGs could potentially affect the clinical efficacy of different batches of these polyclonal antibody preparations. METHODS: Four batches of ATG-Fresenius and Thymoglobulin were compared regarding their capacity to interact with human leukocytes from healthy donors and kidney transplant recipients. Using flow cytometric assays, we analyzed the reactivity of these ATG preparations with Jurkat cells and with primary leukocytes. In addition, ATGs derived from different batches were probed with a panel of cell lines expressing high levels of ATG antigens. Their ability to mediate complement-mediated lysis of human monocytes and lymphocytes was also compared. RESULTS: Binding studies to leukocyte antigens and functional analysis pointed to a high conformity among different batches in both ATG preparations. CONCLUSIONS: From our in vitro data, it can be expected that ATGs derived from different batches will not differ in their clinical efficacy. Furthermore, the methods described in this study allow for a reliable analysis of ATG batches.
BACKGROUND: Antithymocyte globulins (ATGs) are used to prevent and treat allograft rejection and graft versus host disease. They are purified IgG fractions derived from rabbits immunized with the Jurkat T-cell line (ATG-Fresenius) or thymus cells (Thymoglobulin). Differences not only in the amounts of leukocyte reactive antibodies but also in the antigens targeted by ATGs could potentially affect the clinical efficacy of different batches of these polyclonal antibody preparations. METHODS: Four batches of ATG-Fresenius and Thymoglobulin were compared regarding their capacity to interact with human leukocytes from healthy donors and kidney transplant recipients. Using flow cytometric assays, we analyzed the reactivity of these ATG preparations with Jurkat cells and with primary leukocytes. In addition, ATGs derived from different batches were probed with a panel of cell lines expressing high levels of ATG antigens. Their ability to mediate complement-mediated lysis of human monocytes and lymphocytes was also compared. RESULTS: Binding studies to leukocyte antigens and functional analysis pointed to a high conformity among different batches in both ATG preparations. CONCLUSIONS: From our in vitro data, it can be expected that ATGs derived from different batches will not differ in their clinical efficacy. Furthermore, the methods described in this study allow for a reliable analysis of ATG batches.
Authors: Lisa V E Oostenbrink; Cornelia M Jol-van der Zijde; Katrine Kielsen; Anja M Jansen-Hoogendijk; Marianne Ifversen; Klaus G Müller; Arjan C Lankester; Astrid G S van Halteren; Robbert G M Bredius; Marco W Schilham; Maarten J D van Tol Journal: Front Immunol Date: 2019-03-06 Impact factor: 7.561
Authors: Sheila M Keating; Rena A Mizrahi; Matthew S Adams; Michael A Asensio; Emily Benzie; Kyle P Carter; Yao Chiang; Robert C Edgar; Bishal K Gautam; Ashley Gras; Jackson Leong; Renee Leong; Yoong Wearn Lim; Vishal A Manickam; Angelica V Medina-Cucurella; Ariel R Niedecken; Jasmeen Saini; Jan Fredrik Simons; Matthew J Spindler; Kacy Stadtmiller; Brendan Tinsley; Ellen K Wagner; Nicholas Wayham; LaRee Tracy; Carina Vingsbo Lundberg; Dirk Büscher; Jose Vicente Terencio; Lucy Roalfe; Emma Pearce; Hayley Richardson; David Goldblatt; Anushka T Ramjag; Christine V F Carrington; Graham Simmons; Marcus O Muench; Steven M Chamow; Bryan Monroe; Charles Olson; Thomas H Oguin; Heather Lynch; Robert Jeanfreau; Rachel A Mosher; Matthew J Walch; Christopher R Bartley; Carl A Ross; Everett H Meyer; Adam S Adler; David S Johnson Journal: Nat Biotechnol Date: 2021-04-15 Impact factor: 54.908