Journal
LEUKEMIA & LYMPHOMA
Volume 48, Issue 12, Pages 2424-2436Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10428190701647879
Keywords
rituximab resistance; CD52; alemtuzamab; complement-mediated cytotoxicty; non-Hodgkin lymphoma
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Funding
- NATIONAL CANCER INSTITUTE [P01CA103985] Funding Source: NIH RePORTER
- NCI NIH HHS [P01 CA103985-1] Funding Source: Medline
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In an attempt to define mechanisms by which B-cell non-Hodgkin lymphoma (NHL) may escape rituximab immunotherapy, we developed several rituximab-resistant cell lines (RRCL) generated from the rituximab-sensitive cell lines (RSCL) Raji and RL. Rituximab resistance was associated with CD20 downregulation and upregulation of CD52 and the complement inhibitory proteins (CIPs) CD55 and CD59. No significant alemtuzumab-associated complement-mediated cell lysis (CMC) or antibody-dependent cellular cytotoxicity ( ADCC) was demonstrated in RSCL. In contrast, in vitro exposure of RRCL to alemtuzumab resulted in a significant degree of CMC and ADCC. Of note, in vitro blocking of CD52 with anti-CD52 F(ab')(2) fractions in RRCL improved rituximab-associated CMC as compared to unblocked RRCL. Our current data provides a basis for further evaluation of alemtuzumab-based clinical trials for patients with rituximab-resistant NHL.
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