Abstract
Rituximab has shown great efficacy in B-cell non-Hodgkin's lymphoma (NHL), by binding CD20 to induce cell destruction through activating apoptosis, complement and cell-mediated cytotoxity. However, the response rate of patients with relapsed or refractory CD20-positive NHL to standard rituximab treatment is less than 50%, and the non-responders, especially DLBCL patients, still could express high levels of CD20. Therefore, a translational in vivo platform to understand the mechanisms behind Rituximab resistance is in urgent need. We established and characterized a series of DLBCL lymphoma PDX. Eleven non-GCB DLBCL PDX models were selected for the Rituximab efficacy study, of which 3 are relapse DLBCL. IHC and RNAseq were conducted to evaluate CD20 status and expression of other genes. The anti-tumor efficacy of Rituximab in 11 PDX models revealed that 5 of them were sensitive to rituximab and 6 had a poor response. All these models are CD20 positive judged by IHC. By analyzing the correlation of tumor growth inhibition (TGI) and the genomic background of these PDX models, we identified several candidate genes such as BCL2L1, PDK1, TGF-β, Lgalsl and p56/p53Lyn that may contribute to drug resistance mediated by elevated apoptotic threshold, modulation of complement activity or diminished cellular cytotoxicity. Further validation studies are in progress. We established a series of DLBCL lymphoma PDX; with advanced genomic profiling method and validation, these models can be precisely used for subtype-specific therapy evaluation and the investigation of the mechanism of drug resistance.
Citation Format: Hui Qi, Xuzhen Tang, Zhiyuan Zou, Ying Fang, Li Wang, Weili Zhao, Qingyang Gu, Qunsheng Ji. A comprehensive DLBCL lymphoma PDX collection to evaluate the efficacy and resistant mechanism of rituximab [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1666.
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