Samsung Medical Center Identifies New Mechanism of Rituximab Resistance in Lymphoma Treatment

CD20-Positive Extracellular Vesicles in Blood Impair Antibody Therapy Efficacy
Potential Prognostic Biomarker Proposed Based on Pre-Treatment Blood Test

Samsung Medical Center announced on July 23 that a research team led by Professor Kim Seokjin of the Department of Hematology and Oncology has identified a new mechanism of resistance to the targeted anticancer drug rituximab in diffuse large B-cell lymphoma (DLBCL), and has proposed the potential of a blood biomarker that could predict treatment response. The results were published in the latest issue of the international journal 'Blood Cancer' specializing in hematologic malignancies.

Research team that elucidated a new mechanism of resistance to the lymphoma treatment rituximab. Samsung Medical Center

The research team discovered a new resistance mechanism in which CD20-positive extracellular vesicles secreted by tumor cells act as 'antigen decoys' by binding to rituximab before the antibody can reach actual tumor cells, thereby interfering with its effect. Four-dimensional optical microscopy observations confirmed that rituximab bound more strongly to the extracellular vesicles than to the cancer cell surfaces, resulting in reduced antibody binding to the tumor cells themselves.

By quantitatively analyzing CD20-positive extracellular vesicles in the serum of newly diagnosed diffuse large B-cell lymphoma patients, the researchers found that in both the training cohort and the independent validation cohort, patients with higher pre-treatment levels of CD20-positive extracellular vesicles had significantly lower disease-specific and overall survival rates. This prognostic predictive power remained independently significant even after adjustment for the International Prognostic Index (IPI).

Cell experiments further revealed that tumor-derived CD20-positive extracellular vesicles promoted the proliferation of lymphoma cells and decreased both the anticancer efficacy of rituximab and immune cell-mediated cytotoxicity.

Professor Kim stated, "This study demonstrates a new resistance mechanism in which extracellular vesicles in the blood bind to therapeutic antibodies and diminish their antitumor effect on tumor cells. We have also suggested the potential to develop a biomarker capable of predicting response to rituximab and prognosis through a simple pre-treatment blood test. We expect that this will provide a foundation for advancing new therapeutic strategies to enhance antibody treatment effects and for the development of precision medicine in the future."

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