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      Revolutionizing cancer immunotherapy: unleashing the potential of bispecific antibodies for targeted treatment

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          Abstract

          Recent progressions in immunotherapy have transformed cancer treatment, providing a promising strategy that activates the immune system of the patient to find and eliminate cancerous cells. Bispecific antibodies, which engage two separate antigens or one antigen with two distinct epitopes, are of tremendous concern in immunotherapy. The bi-targeting idea enabled by bispecific antibodies (BsAbs) is especially attractive from a medical standpoint since most diseases are complex, involving several receptors, ligands, and signaling pathways. Several research look into the processes in which BsAbs identify different cancer targets such angiogenesis, reproduction, metastasis, and immune regulation. By rerouting cells or altering other pathways, the bispecific proteins perform effector activities in addition to those of natural antibodies. This opens up a wide range of clinical applications and helps patients with resistant tumors respond better to medication. Yet, further study is necessary to identify the best conditions where to use these medications for treating tumor, their appropriate combination partners, and methods to reduce toxicity. In this review, we provide insights into the BsAb format classification based on their composition and symmetry, as well as the delivery mode, focus on the action mechanism of the molecule, and discuss the challenges and future perspectives in BsAb development.

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          Understanding the tumor immune microenvironment (TIME) for effective therapy

          The clinical successes in immunotherapy have been both astounding and at the same time unsatisfactory. Countless patients with varied tumor types have seen pronounced clinical response with immunotherapeutic intervention; however, many more patients have experienced minimal or no clinical benefit when provided the same treatment. As technology has advanced, so has the understanding of the complexity and diversity of the immune context of the tumor microenvironment and its influence on response to therapy. It has been possible to identify different subclasses of immune environment that have an influence on tumor initiation and response and therapy; by parsing the unique classes and subclasses of tumor immune microenvironment (TIME) that exist within a patient’s tumor, the ability to predict and guide immunotherapeutic responsiveness will improve, and new therapeutic targets will be revealed.
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            Oncology meets immunology: the cancer-immunity cycle.

            The genetic and cellular alterations that define cancer provide the immune system with the means to generate T cell responses that recognize and eradicate cancer cells. However, elimination of cancer by T cells is only one step in the Cancer-Immunity Cycle, which manages the delicate balance between the recognition of nonself and the prevention of autoimmunity. Identification of cancer cell T cell inhibitory signals, including PD-L1, has prompted the development of a new class of cancer immunotherapy that specifically hinders immune effector inhibition, reinvigorating and potentially expanding preexisting anticancer immune responses. The presence of suppressive factors in the tumor microenvironment may explain the limited activity observed with previous immune-based therapies and why these therapies may be more effective in combination with agents that target other steps of the cycle. Emerging clinical data suggest that cancer immunotherapy is likely to become a key part of the clinical management of cancer. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy.

              Cancer immunotherapy can induce long lasting responses in patients with metastatic cancers of a wide range of histologies. Broadening the clinical applicability of these treatments requires an improved understanding of the mechanisms limiting cancer immunotherapy. The interactions between the immune system and cancer cells are continuous, dynamic, and evolving from the initial establishment of a cancer cell to the development of metastatic disease, which is dependent on immune evasion. As the molecular mechanisms of resistance to immunotherapy are elucidated, actionable strategies to prevent or treat them may be derived to improve clinical outcomes for patients.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2477236Role: Role:
                URI : https://loop.frontiersin.org/people/2556548Role: Role:
                Role:
                URI : https://loop.frontiersin.org/people/1049276Role: Role:
                URI : https://loop.frontiersin.org/people/2349999Role: Role: Role:
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                01 December 2023
                2023
                : 14
                : 1291836
                Affiliations
                [1] 1 West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu, China
                [2] 2 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu, China
                Author notes

                Edited by: Prakash Radhakrishnan, University of Nebraska Medical Center, United States

                Reviewed by: Jeong A. Park, Inha University Hospital, Republic of Korea; Liang Gong, Chinese Academy of Sciences (CAS), China

                *Correspondence: Guobo Shen, shenguobo@ 123456126.com ; Na Xie, naxie@ 123456scu.edu.cn

                †These authors have contributed equally to this work

                Article
                10.3389/fimmu.2023.1291836
                10722299
                38106416
                a070c47a-8526-46d5-9ef4-e8b4aa2a4ef4
                Copyright © 2023 Guo, Wu, Xue, Xie and Shen

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 September 2023
                : 08 November 2023
                Page count
                Figures: 6, Tables: 2, Equations: 0, References: 303, Pages: 33, Words: 14154
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from theNational Key R&D Program of China (2020YFA0509400), Guangdong Basic and Applied Basic Research Foundation (2019B030302012), National Natural Science Foundation of China (81821002, 82130082, 82341004), and 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYGD22007), Sichuan Science and Technology Program (2021YFH0002, 2023NSFSC1878).
                Categories
                Immunology
                Review
                Custom metadata
                Cancer Immunity and Immunotherapy

                Immunology
                bispecific antibodies,immunotherapy,targeted therapy,tumor microenvironment,cancer
                Immunology
                bispecific antibodies, immunotherapy, targeted therapy, tumor microenvironment, cancer

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