![]() ![]() Chemotherapy-induced thrombocytopenia (CIT, platelet count ≤ 100,000/μL after chemotherapy), occurs in approximately 16%–30% of patients receiving platinum-, taxane-, or gemcitabine-based regimens. Thrombocytopenia frequently occurs in patients with cancer because of chemotherapy, the malignancy itself, or infection. Our findings suggest that 2R13 is a promising therapeutic agent for CIT treatment. The platelets produced by 2R13 sustained a higher count than that achieved using seven consecutive injections of rhTPO. ![]() Injection of 5-fluorouracil considerably reduced the platelet count by day 4, which was recovered by 2R13. The platelet count was increased by a single injection of 2R13 for up to 14 days. 2R13 stimulated megakaryocyte differentiation, evidenced by increasing the proportion of high-ploidy (≥ 8N) megakaryocytes in peripheral blood-CD34 + cells. We found that 2R13 specifically interacted with MPL and activated its signaling pathways. The platelet counts were monitored twice a week over 14 days post-initiation of treatment with a single injection of 2R13, or recombinant human TPO (rhTPO) for seven consecutive days. The 2R13-induced platelet production was examined in 8- to 10-week-old wild-type BALB/c female mice and a thrombocytopenia mouse model established by intraperitoneal injection of 5-fluorouracil (150 mg/kg). The effect of 2R13 on megakaryocyte differentiation was evaluated in peripheral blood CD34 + cells by analyzing megakaryocyte-specific differentiation markers (CD41a + and CD42b +) and DNA ploidy using flow cytometry. We identified 2R13 as the most active clone among the binding antibodies via cell proliferation assay using BaF3/MPL cells. MethodsĪnti-MPL antibodies were selected from the human combinatorial antibody phage libraries using phage display. Therefore, the development of effective MPL agonists for treating CIT needs to be further expanded. Although several MPL agonists have been developed to regulate thrombopoiesis, none have been approved for the management of CIT due to concerns regarding efficacy or safety. Thrombopoietin (TPO) and its receptor, myeloid proliferative leukemia (MPL) protein, play a major role in platelet production. Thus, rapid recovery and continuous maintenance of platelet count during chemotherapy cycles are crucial in patients with CIT. Chemotherapy-induced thrombocytopenia (CIT) leads to dose reduction and treatment delays, lowering chemotherapy efficacy and survival rate. Thrombocytopenia is a common complication in cancer patients undergoing chemotherapy. ![]()
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