%0 Journal Article
%T Anti-CD47 immunotherapy in combination with BCL-2 inhibitor to enhance anti-tumor activity in B-cell lymphoma.
%A Li M
%A Yu H
%A Qi F
%A Ye Y
%A Hu D
%A Cao J
%A Wang D
%A Mi L
%A Wang Z
%A Ding N
%A Ping L
%A Shu S
%A Zhu J
%J Hematol Oncol
%V 40
%N 4
%D Oct 2022
%M 35477179
%F 4.85
%R 10.1002/hon.3009
%X CD47 expressed on cancer cells enables macrophage immune evasion. Blocking CD47 using anti-CD47 monoclonal antibodies (mAbs) is a promising strategy. The anti-CD47 mAb TJC4 has anti-tumor activity but lacks hematological toxicity. Venetoclax, a B-cell lymphoma 2 (BCL-2) inhibitor for B-cell malignancy, induces phosphatidylserine (PS) extracellular exposure, representing an "eat-me" signal for macrophages. The present study aimed to explore whether TJC4-Venetoclax combined therapy exerts synergistic anti-cancer properties in B-cell lymphoma. In vitro, flow cytometry and microscopy assessed whether TJC4 monotherapy or combination treatment could promote macrophage-mediated phagocytosis of tumor cells. Induced PS exposure on the cell membrane was measured using flow cytometry with Annexin V-FITC staining. In vivo, Venetoclax and TJC4's synergistic anti-tumor effects were evaluated. B cell lymphoma cell lines express high levels of CD47 and patients with diffuse large B cell lymphoma expressing CD47 have a worse clinical prognosis. TJC4 eliminates tumor cells via macrophage-mediated phagocytosis. In vitro and in vivo, the TJC4-Venetoclax combination increased phagocytosis significantly compared with either agent alone, showing synergistic phagocytosis, and displayed synergistic anti-cancer properties in B-cell lymphoma. Our results support the TJC4-Venetoclax combination as a promising therapy, and suppressing BCL-2 and CD47 simultaneously could represent a novel therapeutic paradigm for B-cell lymphoma.