Structural basis for bispecific antibody design: arrangement of domain linkage produces activity enhancement DOI
K Sato,

Shiro Uehara,

Atsushi Tsugita

и другие.

Опубликована: Апрель 25, 2024

Abstract A bispecific antibody (BsAb) is a protein genetically engineered from two different antibodies, allowing simultaneous binding to kinds of antigen bring them into close proximity. BsAbs have been developed as anti-cancer drugs that accumulate lymphocytes onto cancer cells by bridging antigens present on each. Ex3 diabody composed the fused variable regions (Fvs) an anti-epidermal growth factor receptor (EGFR) and anti-CD3 with potent cytotoxic activity. In Ex3, LH-type, in which light chain (VLs) are located at N-terminus those heavy (VHs), exerted 1000-fold greater anticancer activity than HL-type, VHs VLs. This effect (termed ‘activity enhancement’), greatly enhanced domain rearrangement, has reported not only for but also several other BsAbs. However, molecular details this enhancement yet be elucidated. study, we determined cryo-EM structures LH- HL-types complex CD3 EGFR. Structural comparison showed rearrangement linkage produces drastic structural differences overall shape these complexes, dynamics attributed flexibility between Fvs. These findings provide valuable insights mechanism study will stepping stone towards establishing design foundation BsAb development.

Язык: Английский

Single-cell sequencing unveils the transcriptomic landscape of castration-resistant prostate cancer-associated fibroblasts and their association with prognosis and immunotherapy response DOI Creative Commons
Yi‐Feng Qiu, Yuhan Wang,

Jiahe Liu

и другие.

BMC Cancer, Год журнала: 2025, Номер 25(1)

Опубликована: Апрель 30, 2025

Язык: Английский

Процитировано

0
Reprogramming of regulatory T cells in inflammatory tumor microenvironment: can it become immunotherapy turning point? DOI Creative Commons
Jinming Liu, Biao Zhang, Guolin Zhang

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Фев. 21, 2024

Overcoming the immunosuppressive tumor microenvironment and identifying widely used immunosuppressants with minimal side effects are two major challenges currently hampering cancer immunotherapy. Regulatory T cells (Tregs) present in almost all tissues play an important role preserving autoimmune tolerance tissue homeostasis. The inflammatory causes reprogramming of Tregs, resulting conversion Tregs to phenotypes. This process ultimately facilitates immune escape or progression. However, current systemic Treg depletion therapies may lead severe toxicity. Therefore, it is crucial understand mechanism develop immunotherapies that selectively target within tumors. article provides a comprehensive review potential mechanisms involved cell explores application interference pathways has shown promise reducing number tumor-associated impairing their function during immunotherapy, thereby improving anti-tumor responses. Furthermore, deeper understanding drive could reveal new molecular targets for future treatments.

Язык: Английский

Процитировано

3
Hepatitis B virus X protein and TGF-β: partners in the carcinogenic journey of hepatocellular carcinoma DOI Creative Commons

Wei Yan,

Dean Rao,

Feimu Fan

и другие.

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Июнь 19, 2024

Hepatitis B infection is substantially associated with the development of liver cancer globally, prevalence hepatocellular carcinoma (HCC) cases exceeding 50%. virus (HBV) encodes X (HBx) protein, a pleiotropic regulatory protein necessary for transcription HBV covalently closed circular DNA (cccDNA) microchromosome. In previous studies, HBV-associated HCC was revealed to be affected by HBx in multiple signaling pathways, resulting genetic mutations and epigenetic modifications proto-oncogenes tumor suppressor genes. addition, transforming growth factor-β (TGF-β) has dichotomous potentials at various phases malignancy as it crucial pathway that regulates cellular physiological processes. early HCC, TGF-β significant antitumor effect, whereas advanced promotes malignant progression. interacts regulating pathogenesis HCC. This review summarizes respective combined functions TGB-β occurrence development.

Язык: Английский

Процитировано

3
Exploring the potential of TGFβ as a diagnostic marker and therapeutic target against cancer DOI Creative Commons
Pankaj Kumar Garg, Siddhika Pareek, Prakash Kulkarni

и другие.

Biochemical Pharmacology, Год журнала: 2024, Номер 231, С. 116646 - 116646

Опубликована: Ноя. 20, 2024

Язык: Английский

Процитировано

3
Recent advances in therapeutic use of transforming growth factor-beta inhibitors in cancer and fibrosis DOI Creative Commons
Jing He, Yan Gao, Linyuan Jing

и другие.

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Апрель 25, 2025

Transforming growth factor-beta (TGF-β) has long been known to be associated with early embryonic development and organogenesis, immune supervision, tissue repair homeostasis in adults. TGF-β complex roles fibrosis cancer that may opposing at different stages of these diseases. Under pathological conditions, overexpression causes epithelial-mesenchymal transition, deposition extracellular matrix, formation cancer-associated fibroblasts, leading fibrotic disease or cancer. Fibroblasts, epithelial cells, cells are the most common targets TGF-β, while TGF-β-associated Given critical role its downstream molecules progression cancer, therapies targeting signaling appear a promising strategy. Preclinical clinical studies have investigated including antisense oligonucleotides, monoclonal antibodies, ligand traps. However, targeted therapy hindered by systemic cytotoxicity. This review discusses molecular mechanisms highlights for as therapeutic strategy related

Язык: Английский

Процитировано

0
Single-cell and bulk RNA sequencing analysis of B cell marker genes in TNBC TME landscape and immunotherapy DOI Creative Commons

Fangrui Zhao,

Chen Zhao,

Tangpeng Xu

и другие.

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Дек. 4, 2023

This study amied to investigate the prognostic characteristics of triple negative breast cancer (TNBC) patients by analyzing B cell marker genes based on single-cell and bulk RNA sequencing.

Язык: Английский

Процитировано

6
Introduction of Carbonyl Groups into Antibodies DOI Creative Commons
Evgeny L. Gulyak, Vera A. Alferova, Vladimir A. Korshun

и другие.

Molecules, Год журнала: 2023, Номер 28(23), С. 7890 - 7890

Опубликована: Дек. 1, 2023

Antibodies and their derivatives (scFv, Fabs, etc.) represent a unique class of biomolecules that combine selectivity with the ability to target drug delivery. Currently, one most promising endeavors in this field is development molecular diagnostic tools antibody-based therapeutic agents, including antibody–drug conjugates (ADCs). To meet challenge, it imperative advance methods for modifying antibodies. A particularly strategy involves introduction carbonyl groups into antibody are amenable further modification by biorthogonal reactions, namely aliphatic, aromatic, α-oxo aldehydes, as well aliphatic aryl–alkyl ketones. In review, we summarize preparation applications site-specific synthesized using approach.

Язык: Английский

Процитировано

4
Copper homeostasis and cuproptosis in gynecological cancers DOI Creative Commons
Xiaodi Huang,

Mengyi Lian,

Changzhong Li

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Сен. 25, 2024

Copper (Cu) is an essential trace element involved in a variety of biological processes, such as antioxidant defense, mitochondrial respiration, and bio-compound synthesis. In recent years, novel theory called cuproptosis has emerged to explain how Cu induces programmed cell death. targets lipoylated enzymes the tricarboxylic acid cycle subsequently triggers oligomerization dihydrolipoamide S-acetyltransferase, leading loss Fe–S clusters induction heat shock protein 70. Gynecological malignancies including cervical cancer, ovarian cancer uterine corpus endometrial carcinoma significantly impact women’s quality life even pose threat their lives. Excessive can promote progression by enhancing tumor growth, proliferation, angiogenesis metastasis through multiple signaling pathways. However, there are few studies investigating gynecological cancers relation cuproptosis. Therefore, this review discusses homeostasis while exploring potential use for prognosis prediction well its implications treatment cancers. Additionally, we explore application ionophore therapy treating malignancies.

Язык: Английский

Процитировано

1
Development of a Bispecific IgG1 Antibody Targeting BCMA and PDL1 DOI Creative Commons
Irene Cattaneo, Sylvie Choblet, Rut Valgardsdottir

и другие.

Antibodies, Год журнала: 2024, Номер 13(1), С. 15 - 15

Опубликована: Фев. 20, 2024

We designed, produced, and purified a novel IgG1-like, bispecific antibody (bsAb) directed against B-cell maturation antigen (BCMA), expressed by multiple myeloma (MM) cells, an immune checkpoint inhibitor (ICI), PDL1, in the MM microenvironment. The BCMA×PDL1 bsAb was fully characterized vitro. bound specifically simultaneously, with nM affinity, to both native membrane-bound antigens recombinant soluble fragments, as shown immunophenotyping analyses surface plasmon resonance (SPR), respectively. binding affinity of for PDL1 BCMA similar each other, but about 10-fold lower compared parent mAb, probably due steric hindrance associated more internal anti-PDL1 Fab. also able functionally block targets IC50 range. Fc functional, inducing human-complement-dependent cytotoxicity well ADCC NK cells 24 h killing assays. Finally, effective 7-day assays peripheral blood mononuclear effectors, up 75% target cell line at physiologically attainable, 6 nM, concentration. These data provide necessary basis future optimization vivo testing this bsAb.

Язык: Английский

Процитировано

1
From immune equilibrium to tumor ecodynamics DOI Creative Commons
Xiaoping Chen

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Май 10, 2024

Objectives There is no theory to quantitatively describe the complex tumor ecosystem. At same time, cancer immunotherapy considered a revolution in oncology, but methods used tumors and criteria evaluate efficacy are not keeping pace. The purpose of this study establish new for describing ecosystem, innovating characterization, establishing evaluation immunotherapy. Methods Based on mathematization immune equilibrium establishment immunodynamics previous study, method reverse was used, namely, braking force regarded as ecological force, concept momentum physics applied ecosystem series ecodynamic equations. These equations were solve fundamental problems Results A established. their component factors could be distinguish disease progression, pseudoprogression, hyperprogression On basis, adjusted established achieve equivalence activity (including immunosuppressive metabolic activity) volume, which calculate individual remission rate (ieRECIST) solid based ecodynamics. moving cube-to-force square ratio its expression proposed area under curve blood required an when known. Conclusions termed ecodynamics emphasizing both volume basic It can predicted that future will era ecotherapy targets entire

Язык: Английский

Процитировано

0