Recent updates on Sintilimab in solid tumor immunotherapy
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Recent updates on Sintilimab in solid tumor immunotherapy Xuhong Liu1 and Yong Yi2*
Abstract In recent years, there have been advancements in traditional patterns of tumor therapy with the adoption of immunotherapy. Its application with or without other combined regimens has attracted attention from clinicians. Sintilimab (Tyvyt®), a highly selective fully human IgG4 monoclonal antibody, blocks the binding site of programmed cell death protein 1 (PD-1), thereby, inhibiting the interaction between PD-1 and its ligands (PD-L1/2) to restore the endogenous anti-tumor T cell responses. Sintilimab has been proven to be clinically beneficial in multiple solid tumor therapies. Combination therapy and monotherapy have shown potential and encouraging anti-tumor efficacy with controllable and acceptable toxicities. The combination therapy is more likely to be a novel and promising therapeutic option. This study provides an overview of the status of sintilimab-based clinical trials in various solid tumors. Keywords: Solid tumors, Sintilimab, PD-1 inhibitor, Immunotherapy, Clinical Progress
Introduction Immune checkpoint proteins, including PD-1 and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), initiate signaling pathways that suppress T-cell anti-tumor effect [1]. Following the binding of immune checkpoint inhibitors (ICIs) to immune checkpoint proteins on the surface of T cells, tumor-mediated immune suppression is reversed [2]. Currently, clinical application of ICIs are mainly focused on anti-CTLA4 antibodies (ipilimumab, tremelimumab), anti-PD-1 antibodies (pembrolizumab, nivolumab, cemiplimab) and anit-PD-L1 antibodies (atezolizumab, avelumab and durvalumab). Hence, ICIs have immensely revolutionized and transformed cancer therapeutic modes [1, 3]. Sintilimab (Innovent Biologics, Suzhou, China), a type of PD-1 antibodies originally co-developed by Innovent Biologics, Eli Lilly and Company, has been approved for * Correspondence: [email protected] 2 Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Key Laboratory for Carcinogenesis & Cancer Invasion, The Chinese Ministry of Education, Fudan University, Shanghai 200032, China Full list of author information is available at the end of the article
clinical management of either relapsed or refractory classical Hodgkin’s lymphoma (RR-c-HL)after more than second-line systematic chemotherapy [4]. Notably, Sintilimab was included in the 2019 edition of The Lymphoma Diagnosis and Treatment Guide of The Chinese Society of Clinical Oncology [4].
Preclinical efficacy of Sintilimab Immune activation effects are maximized when immune checkpoint receptors are blocked and reach their saturation. This is mediated by both the concentration and the affinity of the antibody to the receptor. Despite antiPD-1 antibodies (pembrolizumab (Keytruda, MK-3475) and nivolumab (Opdivo, MDX-1106)) exhibiting the highest affinity for human PD-1 and a lower off-rate, the PD-1 receptor occupancy of sintilimab on circulating T cells is superior,
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