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Patients with follicular lymphoma at the time of diagnosis were CD20 positive (A). Neoplastic follicles replaces nodal architecture with back-to-back pattern (HES X 1) (A1). Low grade (1-2) with a predominance of centrocytes (HES X20) (A2). CD20 positive B cells are seen in both follicular and interfollicular areas (HES X 20) (A3). Staining CD10 (A4) and BCL2 (A5) were found positive within the follicles and also infiltrate interfollicular areas (HES X20). Follicular lymphoma (X10) of the same patient at relapse and after anti-CD20 therapy (rituximab) with loss of CD20 (B). Neoplastic follicles in low-grade follicular lymphoma, low grade (grade 1-2) with predominance of centrocytes (B1). Neoplastic follicles replaces nodal architecture with back-to-back pattern (HES X 10). Immunohistochemistry with immunoperoxidase stains in paraffin sections shows CD20 negative B cells (B2). The other B cell markers CD79A (B3), PAX5 (B4), and BCL6 (B5) remain positively expressed by follicular lymphoma cells.
Source publication
Aim: Anti-CD20 monoclonal antibody is a cornerstone therapy for follicular lymphoma. Following anti-CD20 therapy, a potential decrease in CD20 antigen, and therefore a loss of the tumor target might be expected. However, the incidence and clinical significance of CD20 loss on tumor cells in patients with relapsed or refractory follicular lymphoma a...
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Background
Odronextamab is a hinge-stabilised, fully human IgG4-based CD20 × CD3 bispecific antibody that binds CD3 on T cells and CD20 on B cells. We aimed to evaluate the safety and antitumour activity of odronextamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma.
Methods
This single-arm, multicentre, phase 1, dose-escalati...
Citations
... The other study found that CD20 loss occurred in 16% of R/R FL patients, whose median OS was significantly shorter than that of CD20-positive patients (8.9 months vs. 28.3 months) (24). These results indicated that CD20 loss was related to a poor prognosis of B-NHL. ...
Background
Follicular lymphoma (FL), a common indolent B-cell lymphoma, has the potential to transform into an aggressive lymphoma, such as diffuse large B-cell lymphoma (DLBCL). The outcome of patients with transformed follicular lymphoma (tFL) is poor, especially in patients with transformed lymphoma after chemotherapy and patients with progression within 24 months (POD24). Chimeric antigen receptor (CAR) T-cell therapy combined with autologous stem cell transplantation (ASCT) has promising antitumor efficacy.
Case presentation
Here, we described a 39-year-old male patient who was initially diagnosed with FL that transformed into DLBCL with POD24, CD20 negativity, TP53 mutation, and a bulky mass after 3 lines of therapy, all of which were adverse prognostic factors. We applied a combination approach: CD19 CAR T-cell infusion following ASCT. Ibrutinib was administered continuously to enhance efficacy, DHAP was administered as a salvage chemotherapy, and ICE was administered as a bridging regimen. The patient underwent BEAM conditioning on days -7~ -1, a total of 3.8 × 106/kg CD34⁺ stem cells were infused on days 01~02, and a total of 10⁸ CAR T cells (relmacabtagene autoleucel, relma-cel, JWCAR029) were infused on day 03. The patient experienced grade 2 cytokine release syndrome (CRS), manifesting as fever and hypotension according to institutional standards. There was no immune effector cell-associated neurotoxicity syndrome (ICANS) after CAR T-cell infusion. Finally, the patient achieved CMR at +1 month, which has been maintained without any other adverse effects.
Conclusion
This case highlights the amazing efficacy of CD19 CAR T-cell therapy following ASCT for R/R tFL, thus providing new insight on therapeutic strategies for the future.
... [17][18][19] Similarly, loss of CD20 upon relapse following rituximab has been reported. [20][21][22][23][24] CD20, encoded by MS4A1, is a member of the membrane-spanning 4-domain family, subfamily A (MS4A), 25,26 which comprises four transmembrane helical domains, two conserved extracellular loops (a small ECL1 loop and a larger ECL2 loop), and intracellular N-and Cterminal sequences. 27,28 Conserved sequences within the ECL2 loop, 170-ANPS-173, are part of a shared epitope for several anti-CD20 agents including, rituximab and obinutuzumab, 28,29 while other anti-CD20 agents such as ofatumumab bind to sequences located in both ECL1 and ECL2. ...
CD20 is an established therapeutic target in B-cell malignancies. The CD20xCD3 bispecific antibody mosunetuzumab has significant efficacy in B-cell non-Hodgkin lymphomas (NHL). Since target antigen loss is a recognized mechanism of resistance, we evaluated the contribution of CD20 expression to clinical response in patients with relapsed and/or refractory NHL in the phase 1/2 GO29781 trial (ClinicalTrials.gov: NCT02500407) investigating mosunetuzumab monotherapy. CD20 was studied using immunohistochemistry (IHC), RNA sequencing, and whole-exome sequencing performed centrally in biopsies collected prior to treatment, or as paired samples at pre-dose and on-treatment, or at-progression. Prior to treatment, most patients exhibited a high proportion of tumor cells expressing CD20; however, the proportion of CD20+ tumor cells in 16/293 (5.5%) patients was <10%. Analyses of paired biopsies from patients during treatment revealed that CD20 levels were maintained in 29/30 (97%), vs patients with samples at-progression, in which 11/32 (34%) showed CD20 loss. Reduced transcription or acquisition of truncating mutations explained most but not all cases of CD20 loss. In vitro modeling confirmed the effect of CD20 variants identified in clinical samples on reduction of CD20 expression and confirmed missense mutations in the extracellular domain that could block mosunetuzumab binding. This study expands knowledge about the occurrence of target antigen loss after anti-CD20 therapeutics to CD20-targeting bispecific antibodies and elucidates the underlying mechanisms for reduced CD20 expression at disease progression that may be generalizable to other anti-CD20 targeting agents. These results also establish the utility of readily-available IHC staining for CD20 as a tool to inform clinical decisions.
... These ligands are plasma membrane phosphoproteins and have deeper connections in the cells while their expression is modified in various diseases and conditions based on the cell and extracellular signals. CD 20 is expressed in a wide range of tumours and autoimmune disorder regulation (6)(7)(8)(9). CD30 expression is found on Hodgkin and Reed-Sternberg cells, anaplastic large-cell lymphoma cells, and activated B or T lymphocytes. CD30 has been shown to be a transmembrane receptor that is significantly homologous to the tumour necrosis factor receptor (TNFR) family (10)(11). ...
... Os ligandos CD20, CD30, CD 40 e CCR5 são expressos na superfície das células B. Estes ligandos são fosfoproteínas da membrana plasmática e têm ligações mais profundas nas células, sendo a sua expressão alterada em várias doenças e condições através de sinais celulares e extracelulares. O CD 20 é expresso numa vasta gama de tumores e na regulação de doenças auto-imunes (6)(7)(8)(9). A expressão de CD30 encontra-se nas células de Hodgkin e Reed-Sternberg, nas células do linfoma anaplásico de grandes células e nos linfócitos B ou T activados. ...
The goal was to evaluate the role of red rose extract (Pierre de Ronsard) on the human B lymphocytes gene CD20, CD30, CD40, and CCR5 expression. Red rose extract was prepared at the dilution of 0.0075% (v/v) and stored until use at -20°C. Cell treatment was performed at 37°C on human B cells. Cells were plated in 6 well plates at 1.5x106 cells per well and stored at -80°C and total RNA extracted. RTq-PCR was performed according to Genecopoeia. The cycle threshold method (ΔΔCt) was used for data analysis. The comparative Ct method quantification (2^-ΔCt ) and fold change for CD20, CD30, CD40 and CCR5 were - 5.65E+01, 4.80E-01, N/A, 2.47E-01; and 0.954,0.377, N/A and 0.577, respectively. The amount of total RNA extracted from about 4.5x10⁶ cells was low and did not allow us to measure the RNA profile. With the exception of CD40, all other genes were expressed and well-measured in both B cell samples by qRT-PCR. The expression of CD30 and CCR5 genes were decreased in B lymphocytes in vitro with the rose extract treatment. More studies are needed to further study these effects and potential.
... In a trial of CD19 targeted CAR T cell therapy in NHL, 5 non-responders were found to have CD19-negative disease (76). Similarly, the loss of CD20 has been reported following rituximab therapy in lymphoma patients (77). Thus, there is an increasing interest in finding novel targets other than CD19 and CD20 for treatment of R/R DLBCL patients. ...
Prognosis for patients with refractory/relapsed (R/R) diffuse large B-cell lymphoma (DLBCL) is poor. Immune-based therapeutic treatments such as CD19 Chimeric Antigen Receptor (CAR) T cell therapies have dramatically changed the treatment landscape for R/R DLBCL leading to durable remissions in ~ 50% of patients. However, there remains an unmet need for developing novel therapies to improve clinical outcomes of patients not responding or relapsing after CAR T cell therapies. Lack of suitable immunotherapeutic targets and disease heterogeneity represent the foremost challenges in this emerging field. In this review, we discuss the recently approved and emerging novel immunotherapies for patients with R/R DLBCL in the post-CAR T era and the cell surface targets currently used.
