ImmunoPET: Concept, Design, and Applications

Chemical Reviews, Journal Year: 2020, Volume and Issue: 120(8), P. 3787 - 3851

Published: March 23, 2020

Immuno-positron emission tomography (immunoPET) is a paradigm-shifting molecular imaging modality combining the superior targeting specificity of monoclonal antibody (mAb) and inherent sensitivity PET technique. A variety radionuclides mAbs have been exploited to develop immunoPET probes, which has driven by development optimization radiochemistry conjugation strategies. In addition, tumor-targeting vectors with short circulation time (e.g., Nanobody) or an enhanced binding affinity bispecific antibody) are being used design novel probes. Accordingly, several such as

Language: Английский

---

Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 28, 2023

Abstract Immune-checkpoint inhibitors (ICBs), in addition to targeting CTLA-4, PD-1, and PD-L1, novel LAG-3 drugs have also been approved clinical application. With the widespread use of drug, we must deeply analyze dilemma agents seek a breakthrough treatment prospect. Over past decades, these demonstrated dramatic efficacy, especially patients with melanoma non-small cell lung cancer (NSCLC). Nonetheless, field broad concept solid tumours, non-specific indications, inseparable immune response side effects, unconfirmed progressive disease, complex regulatory networks resistance are four barriers that limit its Fortunately, successful trials ICB combination therapies, advent era oncolytic virus gene editing, technical mRNA vaccines nano-delivery systems made remarkable breakthroughs currently. In this review, enumerate mechanisms each checkpoint targets, associations between tumour mutation burden, key or signalling pathways, specific evidence efficacy classical targets new among different types put forward dialectical thoughts on drug safety. Finally, discuss importance accurate triage based recent advances predictive biomarkers diagnostic testing techniques.

Language: Английский

---

Cancer immunotherapy with immune checkpoint inhibitors (ICIs): potential, mechanisms of resistance, and strategies for reinvigorating T cell responsiveness when resistance is acquired

Cancer Cell International, Journal Year: 2023, Volume and Issue: 23(1)

Published: April 10, 2023

Abstract Cancer is still the leading cause of death globally. The approval therapeutic use monoclonal antibodies against immune checkpoint molecules, notably those that target proteins PD-1 and PD-L1, has changed landscape cancer treatment. In particular, first-line PD-1/PD-L1 inhibitor drugs are increasingly common for treatment metastatic cancer, significantly prolonging patient survival. Despite benefits brought by inhibitors (ICIs)-based therapy, majority patients had their diseases worsen following a promising initial response. To increase effectiveness ICIs advance our understanding mechanisms causing resistance, it crucial to find new, effective, tolerable combination treatments. this article, we addressed potential solid tumors offer some insight into molecular pathways behind resistance ICIs. We also discuss cutting-edge methods reactivating T-cell responsiveness after been established.

Language: Английский

---

<p>Blocking TGF-β Signaling To Enhance The Efficacy Of Immune Checkpoint Inhibitor</p>

OncoTargets and Therapy, Journal Year: 2019, Volume and Issue: Volume 12, P. 9527 - 9538

Published: Nov. 1, 2019

Abstract: During malignant transformation, a growing body of mutations accumulate in cancer cells which not only drive progression but also endow with high immunogenicity. However, because one or multiple steps cancer-immunity cycle are impaired, anti-cancer immune response is too weak to effectively clear cells. Therefore, how restore robust hot research topic therapeutics field. In the last decade, based on deeper understanding immunity, great signs progress have been made immunotherapies especially checkpoint inhibitors (ICIs). ICIs could block negative co-stimulatory pathways and reactivate tumor-infiltrating lymphocytes (TILs) from exhausted status. exhibit potent effect approved for treatment numerous types. Parallel durable effective tumor control, actual rate unsatisfactory. Although subset patients benefit treatment, large proportion show primary acquired resistance. Previously intensive studies indicated that efficacy was determined by series factors including mutation burden, programmed death ligand-1 (PD-L1) expression, TILs Recently, it reported transforming growth factor-beta (TGF-β) signaling pathway participated escape ICI Concurrent TGF-β blockade might be feasible strategy enhance immunotherapy relieve this mini-review, we summarized latest immunity. Besides, highlighted synergistic ICIs. Keywords: immunotherapy, inhibitor, PD-1, PD-L1, TGF-β, microenvironment, infiltrating lymphocyte

Language: Английский

---

Targeting the tumor microenvironment in B-cell lymphoma: challenges and opportunities

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: Aug. 17, 2021

B-cell lymphoma is a group of hematological malignancies with high clinical and biological heterogeneity. The pathogenesis involves complex interaction between tumor cells the microenvironment (TME), which composed stromal extracellular matrix. Although roles TME have not been fully elucidated, accumulating evidence implies that closely relevant to origination, invasion metastasis lymphoma. Explorations provide distinctive insights for cancer therapy. Here, we epitomize recent advances in discuss its function progression immune escape. In addition, potential value targeting highlighted, expected pave way novel therapeutic strategies.

Language: Английский

---

Humoral and Cellular Response Following Vaccination With the BNT162b2 mRNA COVID-19 Vaccine in Patients Affected by Primary Immunodeficiencies

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Oct. 4, 2021

Mass SARS-Cov-2 vaccination campaign represents the only strategy to defeat global pandemic we are facing. Immunocompromised patients represent a vulnerable population at high risk of developing severe COVID-19 and thus should be prioritized in programs study vaccine efficacy. Nevertheless, most data on efficacy safety available vaccines derive from trials conducted healthy individuals; hence, studies immunogenicity SARS-CoV2 such populations deeply needed. Here, perform an observational longitudinal analyzing humoral cellular response following BNT162b2 mRNA cohort affected by inborn errors immunity (IEI) compared controls (HC). We show that both IEI HC groups experienced significant increase anti-SARS-CoV-2 Abs 1 week after second scheduled dose as well overall statistically expansion Ag-specific CD4+CD40L+ T cells IEI. Five did not develop any specific response, with one these unable also mount response. These raise immunologic concerns about using Ab sole metric protective for SARS-CoV-2. Taken together, findings suggest evaluation vaccine-induced this subpopulation include quantification cells.

Language: Английский

---

Balancing cancer immunotherapy and immune-related adverse events: The emerging role of regulatory T cells

Journal of Autoimmunity, Journal Year: 2019, Volume and Issue: 104, P. 102310 - 102310

Published: Aug. 15, 2019

Language: Английский

---

Cellular and molecular mechanisms breaking immune tolerance in inborn errors of immunity

Cellular and Molecular Immunology, Journal Year: 2021, Volume and Issue: 18(5), P. 1122 - 1140

Published: April 1, 2021

In addition to susceptibility infections, conventional primary immunodeficiency disorders (PIDs) and inborn errors of immunity (IEI) can cause immune dysregulation, manifesting as lymphoproliferative and/or autoimmune disease. Autoimmunity be the prominent phenotype PIDs commonly includes cytopenias rheumatological diseases, such arthritis, systemic lupus erythematosus (SLE), Sjogren's syndrome (SjS). Recent advances in understanding genetic basis diseases suggest an at least partially shared background therefore common pathogenic mechanisms. Here, we explore interconnected pathways autoimmunity immunodeficiency, highlighting mechanisms breaking different layers tolerance self-antigens selected IEI.

Language: Английский

---

New insights into checkpoint inhibitor immunotherapy and its combined therapies in hepatocellular carcinoma: from mechanisms to clinical trials

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(7), P. 2775 - 2794

Published: Jan. 1, 2022

Hepatocellular carcinoma (HCC) is one of the most lethal tumors in China and worldwide, although first-line therapies for HCC, such as atezolizumab bevacizumab, have been effective with good results, researches on new attracted much attention.With deepening research tumor immunology, role operation mechanism immune cells microenvironment (TME) HCC explained, programmed cell death protein 1 (PD-1) binding to ligand could cause T exhaustion reduce IFN-γ secretion, cytotoxic lymphocyte 4 (CTLA-4) CD28 mediate immunosuppression by competing B7 disrupting signal transduction pathway, which also lays foundation development application more checkpoint inhibitors (ICIs).The biological behavior various checkpoints has proved PD-1, (PD-L1), CTLA-4 so on, leading a series clinical trials.Currently, FDA approved nivolumab, pembrolizumab nivolumab plus ipilimumab treatment HCC.However, ICI disadvantages low response rate many side effects, combination ICIs other (such VEGF or VEGFR inhibition, neoadjuvant adjuvant therapy, locoregional therapies) derived.Further studies mechanisms may reveal therapeutic targets future.

Language: Английский

---

The effect of HLA genotype on disease onset and severity in CTLA-4 insufficiency

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 6, 2025

Human Cytotoxic-T-lymphocyte-antigen-4 (CTLA-4) insufficiency caused by heterozygous germline mutations in CTLA4 is a complex immune dysregulation and immunodeficiency syndrome presenting with reduced penetrance variable disease expressivity, suggesting the presence of modifiers that trigger onset severity. Various genetic non-genetic potential triggers have been analyzed CTLA-4 cohorts, however, none them revealed clear association to disease. Multiple HLA haplotypes positively or negatively associated various autoimmune diseases inborn errors immunity (IEI) due relevance MHC strength T cell responses. In this exploratory study, we investigated onset, severity clinical manifestations specific class I (A, B C) II (DRB1 DQB1) alleles forty-three individuals harboring CTLA4. Twenty-six out 43 recruited presented moderate severe symptoms whereas 17 were completely healthy. frequency analysis, odds ratio analysis linkage used. The principal statistical analyses showed no positive between genotypes We found risk associations HLA-DQB1*05:01 HLA-DRB1*01:02 respiratory tract involvement HLA-C*05:01 affection neurological system CTLA-4-insufficient patients. Additionally, protective HLA-DRB1*01:01 gastrointestinal symptoms. Even though, our findings suggest HLA-A, -B, -C, DRB1, DQB1 do not contribute insufficiency, certain HLA-alleles may influence manifestation advocate for further investigation as larger cohorts insufficiency.

Language: Английский

---