Subcellular epithelial protein (HMGB1, p53, RUNX3) expression, alongside expression of CD20, CD4, CD8 and Foxp3 to characterise stromal B lymphocyte, and helper, cytotoxic and regulatory T-lymphocyte cell infiltrate, respectively, was assessed by immunohistochemistry in 218 human tissue samples including normal oesophageal/gastric biopsies (n = 39), BO (non-dysplasia, dysplasia, non-dysplastic background from progressors to dysplasia or cancer, n = 121) and oesophageal adenocarcinoma (n = 58).
Since the first approval of anti-CD20 mAb rituximab in 1997 for the treatment of B-cell malignancies, the market is continuously booming and the clinically used mAbs have undergone a remarkable evolution.
Using a previously described population pharmacokinetic (PK) model of obinutuzumab in patients with non-Hodgkin lymphoma and CLL, we conducted an exposure-response analysis using data from 6 clinical trials in patients with CD20+ B-cell malignancies (CLL11, GADOLIN, GATHER, GAUDI, GAUGUIN and GAUSS) to describe the PK properties of obinutuzumab, identify covariates influencing exposure, and explore how exposure affects safety, efficacy and pharmacodynamics.
Anti-CD20 therapies are a vital component of the treatment of B-cell malignancies, and there is a dynamic therapeutic environment with multiple new data sets reviewed here.
Anti-CD20 monoclonal antibodies (mAbs) rituximab and ofatumumab are potent activators of the classical complement pathway, and have been approved for the treatment of B-cell malignancies.
Targeting both CD20 and phosphatidylinositol 3-kinase (PI3K), a protein that is critically involved in B-cell maturation, could be an efficacious strategy for treating B-cell malignancies.
The tumor cells were positive for CDX-2 and cytokeratin 20 and negative for cytokeratin 7 and thyroid transcription factor-1, consistent with an enteric/colonic-type adenocarcinoma, demonstrating progressive atypia and malignancy.
Although the CD20-targeted monoclonal antibody rituximab (RTX) has revolutionized the therapeutic landscape for B-cell malignancy, relapsed and refractory disease due to RTX resistance continue to constitute major challenges, illustrating the need for better therapies.
The anti-CD20 chimeric monoclonal antibody rituximab has revolutionized the treatment of B-cell malignancies, significantly improving patient clinical outcome.
Combination regimens with anti-CD20 agents might improve the outcomes of patients with relapsed or refractory B-cell malignancies; however, the available comparative clinical evidence is limited.
We therefore developed a strategy to genetically map in vitro drug sensitivity, identifying genes that alter responsiveness to rituximab, a therapeutic anti-CD20 MAb that provides significant benefit to patients with B-cell malignancies.
Both groups were compared by clinical data (age, sex, site, American Joint Committee on Cancer [AJCC] stage, immunosuppression, risk of recurrence, and death during follow-up) and immunochemical features (cytokeratin 20 and 7, thyroid transcription factor 1 [TTF1], p53, large T antigen [CM2B4], CD8 infiltrates).
Rituximab is a chimeric monoclonal antibody directed against B-lymphocyte specific antigen CD20, which is used for the treatment of B-cell malignancies.
Associations of B-cell infiltration, determined by CD20 expression or a B-cell gene-signature, and survival was also analysed in 14 publicly available gene expression datasets of cancer, including the kidney clear cell carcinoma (KIRC) dataset.
In conclusion, RTX-CD47 blocks CD47 "don't eat me" signaling by cancer cells in a CD20-directed manner with essentially no activity towards CD20<sup>neg</sup>/CD47<sup>pos</sup> cells and enhances the activity of therapeutic anticancer antibodies directed to B-cell malignancies.
Here, we report the production of an anti-cancer monoclonal antibody against the CD20 protein from egg whites of transgenic hens, and validated the bio-functional activity of the protein in B-lymphoma and B-lymphoblast cells.
Furthermore, riboswitch functionality to control cellular signaling cascades was demonstrated by using it to specifically induce cell death through the conditionally controlled expression of CD20, which is a target in cancer therapy.