Cross-Reactivity of Antibodies to Rituximab with Other Therapeutic Anti-CD20 Antibodies

• Published in: The Journal of immunology (1950) Vol. 212; no. 4; pp. 529 - 533
• Main Authors: Rispens, Theo, Kuijpers, Taco W, Killestein, Joep, van Kempen, Zoé L E, Bloem, Karien
• Format: Journal Article
• Language: English
• Published: United States 15-02-2024
• Subjects: Antibodies, Monoclonal; Antigens, CD20 - metabolism; Humans; Rituximab - therapeutic use
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.2300647

One reason for a lack of response to rituximab as well as infusion-related anaphylactic adverse events is the development of antidrug Abs to rituximab. Besides rituximab, a number of other therapeutic Abs targeting CD20 are nowadays available as alternatives. In this study, we investigated the potential cross-reactivity of (human) anti-rituximab Abs to three other anti-CD20 mAbs: ofatumumab, obinutuzumab, and ocrelizumab. In 25 cases of anti-rituximab Abs, cross-reactivity was examined using both direct binding assays and inhibition immunoassays. Although no cross-reactivity was observed to ofatumumab or obinutuzumab, 8 of 25 samples also showed reactivity toward ocrelizumab in at least one of the two assays. Furthermore, in three cases of anti-ocrelizumab Abs, cross-reactivity to rituximab was observed in an inhibition immunoassay, albeit not in a direct binding assay. Our results suggest that obinutuzumab or ofatumumab are safe anti-CD20 alternatives in case of the presence of anti-rituximab Abs. It is advisable to proceed cautiously if switching from rituximab to ocrelizumab (or vice versa) is considered in case these alternatives may not be available.