Recently, anti-CD20 (rituximab) and anti-Her2/neu (trastuzumab) antibodies have been developed and applied to the treatment of malignant lymphoma and breast cancer, respectively. However, bulky lymphoma is known to be resistant to rituximab therapy, and this needs to be overcome. Fresh lymphoma cells were collected from 30 patients with non-Hodgkin's lymphoma, the expression of CD20 and CD55 was examined by flow cytometry, and complement-dependent cytotoxicity (CDC) assays were carried out. Susceptibility to CDC with rituximab was decreased in a tumor size-dependent manner (r=-0.895, P<0.0001), but not in a CD20-dependent manner (r=-0.076, P=0.6807) using clinical samples. One complement-inhibitory protein, CD55, contributed to bulky lymphoma-related resistance to CDC with rituximab. A decrease in susceptibility to CDC with rituximab was statistically dependent on CD55 expression (r=-0.927, P<0.0001) and the relationship between tumor size and CD55 expression showed a significant positive correlation (r=0.921, P<0.0001) using clinical samples. To overcome the resistance to rituximab by high expression of CD55 in bulky lymphoma masses, small interfering RNA (siRNA) was designed from the DNA sequence corresponding to nucleic acids 1-380 of the CD55 cDNA. Introduction of this siRNA decreased CD55 expression in the breast cancer cell line SK-BR3 and in CD20-positive cells of patients with recurrent lymphoma; resistance to CDC was also inhibited. This observation gives us a novel strategy to suppress bulky disease-related resistance to monoclonal antibody treatment.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11158893 | PMC |
| http://dx.doi.org/10.1111/j.1349-7006.2006.00139.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Enhancing complement activation by therapeutic anti-tumor antibodies: Mechanisms, strategies, and engineering approaches.
Semin Immunol
December 2024
Department of Immunology, Leiden University Medical Center, Leiden, Netherlands. Electronic address:
The complement system plays an integral role in both innate and adaptive immune responses. Beyond its protective function against infections, complement is also known to influence tumor immunity, where its activation can either promote tumor progression or mediate tumor cell destruction, depending on the context. One such context can be provided by antibodies, with their inherent capacity to activate the classical complement pathway.
View Article and Find Full Text PDFGastric cancer remains a major global health concern with high incidence and mortality rates, particularly in East Asia. Patients often have poor outcomes due to limited treatment efficacy. Zolbetuximab, a monoclonal antibody targeting claudin 18.
View Article and Find Full Text PDFEBV-induced upregulation of CD55 reduces the efficacy of cetuximab treatment in nasopharyngeal carcinoma.
J Transl Med
December 2024
Nasopharyngeal Cancer Center, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, China.
Cetuximab, an anti-epidermal growth factor receptor (EGFR) antibody, has been shown to improve survival in nasopharyngeal carcinoma (NPC) patients. However, a correlation between the expression of EGFR and the response to cetuximab has not been observed, indicating that the mechanism underlying the effects of cetuximab needs to be further elucidated. The antitumour response involves immunotherapeutic mechanisms that target tumour-associated antigens, including complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC), act either alone or, more often, in combination.
View Article and Find Full Text PDFEnhanced Antitumor Immunity of a Globo H-Based Vaccine Enabled by the Combination Adjuvants of 3D-MPL and QS-21.
Angew Chem Int Ed Engl
December 2024
Shanghai Institute of Materia Medica Chinese Academy of Sciences, Carbohydrate-Based Drug Research Center, 555 Zu-Chong-Zhi Road, 201203, Shanghai, CHINA.
Globo H, a specific carbohydrate antigen overexpressed on various human malignancies, has attracted considerable interest as an antigenic target for anticancer vaccine development. Despite several Globo H-based carbohydrate vaccines that have been designed, efficient access to Globo H hexasaccharide antigen and development of powerful adjuvants for enhancing antitumor immunity remain challenging. Herein, we reported a streamlined chemoenzymatic approach to prepare this hexasaccharide antigen, relying on chemical synthesis of Gb5 pentasaccharide by a stereoconvergent [2+3] strategy and subsequent enzymatic α-fucosylation to easily install α1,2-fucose residue.
View Article and Find Full Text PDFThe intestinal flora: The key to unraveling heterogeneity in immune thrombocytopenia?
Blood Rev
December 2024
Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, the Netherlands. Electronic address:
Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by enhanced platelet destruction and impaired platelet production, due to a loss of immune tolerance that leads to targeting of platelets and megakaryocytes by glycoprotein-autoantibodies and/or cytotoxic T cells. There is a high degree of heterogeneity in ITP patients signified by unpredictable disease trajectories and treatment responses. Initial studies in humans have identified intestinal microbiota perturbance in ITP.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!