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      The clinical regimens and cell membrane camouflaged nanodrug delivery systems in hematologic malignancies treatment

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          Abstract

          Hematologic malignancies (HMs), also referred to as hematological or blood cancers, pose significant threats to patients as they impact the blood, bone marrow, and lymphatic system. Despite significant clinical strategies using chemotherapy, radiotherapy, stem cell transplantation, targeted molecular therapy, or immunotherapy, the five-year overall survival of patients with HMs is still low. Fortunately, recent studies demonstrate that the nanodrug delivery system holds the potential to address these challenges and foster effective anti-HMs with precise treatment. In particular, cell membrane camouflaged nanodrug offers enhanced drug targeting, reduced toxicity and side effects, and/or improved immune response to HMs. This review firstly introduces the merits and demerits of clinical strategies in HMs treatment, and then summarizes the types, advantages, and disadvantages of current nanocarriers helping drug delivery in HMs treatment. Furthermore, the types, functions, and mechanisms of cell membrane fragments that help nanodrugs specifically targeted to and accumulate in HM lesions are introduced in detail. Finally, suggestions are given about their clinical translation and future designs on the surface of nanodrugs with multiple functions to improve therapeutic efficiency for cancers.

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          Molecular mechanisms of T cell co-stimulation and co-inhibition.

          Co-stimulatory and co-inhibitory receptors have a pivotal role in T cell biology, as they determine the functional outcome of T cell receptor (TCR) signalling. The classic definition of T cell co-stimulation continues to evolve through the identification of new co-stimulatory and co-inhibitory receptors, the biochemical characterization of their downstream signalling events and the delineation of their immunological functions. Notably, it has been recently appreciated that co-stimulatory and co-inhibitory receptors display great diversity in expression, structure and function, and that their functions are largely context dependent. Here, we focus on some of these emerging concepts and review the mechanisms through which T cell activation, differentiation and function is controlled by co-stimulatory and co-inhibitory receptors.
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            Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells

            Summary Checkpoint inhibitors have revolutionized cancer treatment. However, only a minority of patients respond to these immunotherapies. Here, we report that blocking the inhibitory NKG2A receptor enhances tumor immunity by promoting both natural killer (NK) and CD8+ T cell effector functions in mice and humans. Monalizumab, a humanized anti-NKG2A antibody, enhanced NK cell activity against various tumor cells and rescued CD8+ T cell function in combination with PD-x axis blockade. Monalizumab also stimulated NK cell activity against antibody-coated target cells. Interim results of a phase II trial of monalizumab plus cetuximab in previously treated squamous cell carcinoma of the head and neck showed a 31% objective response rate. Most common adverse events were fatigue (17%), pyrexia (13%), and headache (10%). NKG2A targeting with monalizumab is thus a novel checkpoint inhibitory mechanism promoting anti-tumor immunity by enhancing the activity of both T and NK cells, which may complement first-generation immunotherapies against cancer.
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              Drug Resistance in Cancer: An Overview

              Cancers have the ability to develop resistance to traditional therapies, and the increasing prevalence of these drug resistant cancers necessitates further research and treatment development. This paper outlines the current knowledge of mechanisms that promote or enable drug resistance, such as drug inactivation, drug target alteration, drug efflux, DNA damage repair, cell death inhibition, and the epithelial-mesenchymal transition, as well as how inherent tumor cell heterogeneity plays a role in drug resistance. It also describes the epigenetic modifications that can induce drug resistance and considers how such epigenetic factors may contribute to the development of cancer progenitor cells, which are not killed by conventional cancer therapies. Lastly, this review concludes with a discussion on the best treatment options for existing drug resistant cancers, ways to prevent the formation of drug resistant cancers and cancer progenitor cells, and future directions of study.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2543318/overviewRole: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role:
                Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2186714/overviewRole:
                Role:
                URI : https://loop.frontiersin.org/people/1567125/overviewRole:
                URI : https://loop.frontiersin.org/people/120045/overviewRole: Role: Role: Role: Role:
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                16 April 2024
                2024
                : 15
                : 1376955
                Affiliations
                [1] 1 College of Basic Medicine and Forensic Medicine , Henan University of Science and Technology , Luoyang, Henan, China
                [2] 2 College of Horticulture and Plant Protection , Henan University of Science and Technology , Luoyang, Henan, China
                [3] 3 Luoyang Vocational and Technical College , Luoyang, Henan, China
                Author notes

                Edited by: Feifei Yang, University of Jinan, China

                Reviewed by: Hao Zhang, Jinan University, China

                Ketki Bhise, Biotech Industry, United States

                *Correspondence: Gaofeng Liang, lgfeng990448@ 123456haust.edu.cn
                Article
                1376955
                10.3389/fphar.2024.1376955
                11059051
                38689664
                75368b79-8f24-48bd-9c02-27eb028d6488
                Copyright © 2024 Liu, Yu, Chen, Hu, Fan and Liang.

                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
                : 26 January 2024
                : 02 April 2024
                Funding
                The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This publication was supported by the Key Specialized Research and Development Breakthrough in Henan Province (242102310454), National Key Research and Development Program of China (2022YFE132800) and Key R&D project of Henan Province (221111310600).
                Categories
                Pharmacology
                Review
                Custom metadata
                Pharmacology of Anti-Cancer Drugs

                Pharmacology & Pharmaceutical medicine
                hematologic malignancies,clinical regimens,nanocarrier,nanodrug delivery system,cell membrane camouflage

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