Journal of Immunotoxicology最新文献

Immunophenotypical characterization of immune checkpoint receptor expression in cynomolgus monkeys and human healthy volunteers in resting and in T-cell stimulatory conditions in vitro. 静息和体外t细胞刺激条件下食蟹猴和人类健康志愿者免疫检查点受体表达的免疫表型特征

IF 2.4 4区医学

Journal of Immunotoxicology Pub Date : 2025-12-01 Epub Date: 2025-02-13 DOI: 10.1080/1547691X.2025.2462106

Danielle Craig-Meyer, Joseph A Hollenbaugh, Sara Morgado, Karen McGee, Ethan Perkins, Brogan Yarzabek, Philip Lapinski, Amber Rowse, Chris Cooper, Mara Fortunato, Mario Cocco, Karen Cadwallader, James Munday

{"title":"Immunophenotypical characterization of immune checkpoint receptor expression in cynomolgus monkeys and human healthy volunteers in resting and in T-cell stimulatory conditions in vitro.","authors":"Danielle Craig-Meyer, Joseph A Hollenbaugh, Sara Morgado, Karen McGee, Ethan Perkins, Brogan Yarzabek, Philip Lapinski, Amber Rowse, Chris Cooper, Mara Fortunato, Mario Cocco, Karen Cadwallader, James Munday","doi":"10.1080/1547691X.2025.2462106","DOIUrl":"10.1080/1547691X.2025.2462106","url":null,"abstract":"Immunotherapeutics targeting immune checkpoint receptors or their ligands (i.e., immune checkpoint inhibitors), have been groundbreaking in the field of oncology, radically changing the approach to treatment and improving the clinical outcomes of an ever-expanding list of solid tumors and hematological malignancies. However, immune checkpoint inhibitors (ICI) are not devoid of side effects, collectively regarded as immune-related adverse events (irAE); they are not easily uncovered in preclinical immunotoxicological investigations and are often due to the very low expression of their targets in immunologically-unchallenged non-clinical species. We have characterized expression of a broad range of immune checkpoint receptors in peripheral blood mononuclear cell (PBMC) subpopulations from cynomolgus monkeys and healthy human volunteers, under resting and T-cell stimulatory conditions by multicolor flow cytometry to inform appropriate species selection for modeling potential irAE in immunotherapeutic preclinical research. Focusing on the response of the main lymphocyte populations to interleukin (IL)-2 alone, or in combination with anti-CD3 and anti-CD28 antibodies, checkpoints with shared similarities and key differences between the two species were identified. The results of this first study provide a database for the expression and response to stimulation for immune checkpoint receptors and can help guide future model selection in the design of preclinical studies involving immunotherapeutics directed against these targets.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"22 1","pages":"2462106"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunotoxicological disruption of pregnancy as a new research area in immunotoxicology. 妊娠免疫毒性干扰是免疫毒理学的一个新研究领域。

IF 2.4 4区医学

Journal of Immunotoxicology Pub Date : 2025-12-01 Epub Date: 2025-03-22 DOI: 10.1080/1547691X.2025.2475772

Kazuichi Nakamura

{"title":"Immunotoxicological disruption of pregnancy as a new research area in immunotoxicology.","authors":"Kazuichi Nakamura","doi":"10.1080/1547691X.2025.2475772","DOIUrl":"10.1080/1547691X.2025.2475772","url":null,"abstract":"Immune mechanisms associated with normal pregnancy have only been being substantively investigated since the early 1990s. In parallel with the progress in that area of research, in the past few years it has become increasingly clear that several xenobiotics - including a variety of environmental chemicals, pharmaceuticals, and metals are considered to be both generally immunotoxic and specifically able to affect pregnancy. Among these, there is intense interest regarding potential effects from synthetic cannabinoids, immune checkpoint inhibitors, nanometals, and microplastics, with immunotoxic events that impact on pregnancy being shown for these agents. For instance, phytocannabinoids have been shown to interfere with reproduction in mice through effects on the endocannabinoid system. Because of effects of immune enhancement, as a requirement for regulatory submission, co-inhibitory immune checkpoint molecule inhibitors were also evaluated for effects on pregnancy. Similarly, because of increasing use and concerns about incidental environmental exposures, nanometals, and micro-plastics have also been examined for effects. Several studies in humans or mice showed that exposures to each during gestation increased the risk/rate of fetal loss, in part, by disruption of the placenta-associated immune system. Furthermore, signaling by endogenous danger molecules and/or impairment of physiological intercellular mediators may have contributed to the pregnancy loss. As there are clearly a variety of immunotoxic effects that can impact on a pregnancy, this review attempts to briefly introduce immune mechanisms associated with pregnancy as well as reasons for its loss, and proposes that 'immunotoxicological disruption of pregnancy' be accepted as a new research area in immunotoxicology.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"22 1","pages":"2475772"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The interaction between the expression of CD23 molecule on B- lymphocytes and the level of specific IgE against molecular components of pollen in atopic dermatitis patients with and without dupilumab therapy. 特应性皮炎患者接受或不接受dupilumab治疗时B淋巴细胞CD23分子表达与特异性IgE水平的相互作用

IF 2.4 4区医学

Journal of Immunotoxicology Pub Date : 2025-12-01 Epub Date: 2025-05-28 DOI: 10.1080/1547691X.2025.2507311

J Čelakovská, E Čermáková, P Boudková

{"title":"The interaction between the expression of CD23 molecule on B- lymphocytes and the level of specific IgE against molecular components of pollen in atopic dermatitis patients with and without dupilumab therapy.","authors":"J Čelakovská, E Čermáková, P Boudková","doi":"10.1080/1547691X.2025.2507311","DOIUrl":"https://doi.org/10.1080/1547691X.2025.2507311","url":null,"abstract":"The aim of the study here was to evaluate the association between expression of CD23 molecule on B-lymphocytes and the level of specific IgE to molecular components of birch, Bermuda grass, hazel pollen, timothy, and rye grass in atopic dermatitis (AD) patients (with and without dupilumab therapy). A total of 46 patients suffering from AD were included: 26 without dupilumab treatment and 20 with dupilumab treatment. Serum levels of specific IgE were measured by the components resolved diagnostic assay ALEX2 Allergy Xplorer, the expression of CD23 molecule on B-lymphocytes was evaluated with flow cytometry. For the statistical analysis, the Spearman's rank correlation coefficient was used. In patients treated with dupilumab, the higher association was observed between the expression of CD23 on B-lymphocytes and specific IgE to molecular components Bet v 1, Cor a 1.0103, Cor a 1.0401, and Phl p 1. This study demonstrated that the relationship between CD23 expression on B-lymphocytes and specific IgE to pollen molecular components varies depending on whether the patient was treated with dupilumab and the type of molecular component involved.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"22 1","pages":"2507311"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

No relationship between non-IgE-mediated mechanisms (complement activation or direct activation of mast cells and basophils) during diclofenac etalhyaluronate (SI-613/ONO-5704)-induced anaphylaxis. 在双氯芬酸乙透明质酸（SI-613/ONO-5704）诱导的过敏反应中，非ige介导的机制（补体激活或肥大细胞和嗜碱性粒细胞的直接激活）没有关系。

IF 2.4 4区医学

Journal of Immunotoxicology Pub Date : 2025-12-01 Epub Date: 2025-05-02 DOI: 10.1080/1547691X.2025.2498644

Shuhei Takada, Dai Muramatsu, Yasuaki Isoda, Yamato Sasaki, Kei Toyama, Keiji Yoshioka

{"title":"No relationship between non-IgE-mediated mechanisms (complement activation or direct activation of mast cells and basophils) during diclofenac etalhyaluronate (SI-613/ONO-5704)-induced anaphylaxis.","authors":"Shuhei Takada, Dai Muramatsu, Yasuaki Isoda, Yamato Sasaki, Kei Toyama, Keiji Yoshioka","doi":"10.1080/1547691X.2025.2498644","DOIUrl":"https://doi.org/10.1080/1547691X.2025.2498644","url":null,"abstract":"It was previously reported that half of the anaphylaxis cases occurring after intra-articular administration of diclofenac etalhyaluronate (DEH) - developed as SI-613/ONO-5704 and marketed as JOYCLU® - were induced by IgE-mediated mechanisms; mechanisms for the remaining cases remain unclear. In this study, we investigated the relationship of DEH-induced anaphylaxis to non-IgE-mediated mechanisms in vitro. Assays were carried out based on the production of downstream products of the complement cascade, calcium influx due to Mas-related G protein-coupled receptor-X2 (MRGPRX2) activation, mast cell degranulation, and expression of basophil activation markers. Human plasma, CHO-K1 cells stably expressing MRGPRX2, the human mast cell line LAD2, and the human basophil leukemia cell line KU812 were used for these evaluations. No effect of DEH treatment was found on complement activation, MRGPRX2 agonist activity, direct mast cell activation, or direct basophil activation. From this it could be concluded that DEH-induced anaphylaxis is unlikely to involve complement activation or direct activation of mast cells and basophils. However, the possibility remains that the anaphylaxis might be a non-immunological hypersensitivity reaction due to inhibition of cyclooxygenase-1 by non-steroidal anti-inflammatory drugs (NSAID). Further investigation into the relationship between the non-immunological hypersensitivity and anaphylaxis following DEH administration is warranted.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"22 1","pages":"2498644"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anti-inflammatory effect of Plantago asiatica crude extract in rat gout arthritis model. 车前草粗提物对大鼠痛风关节炎模型的抗炎作用。

IF 2.4 4区医学

Journal of Immunotoxicology Pub Date : 2025-12-01 Epub Date: 2025-02-02 DOI: 10.1080/1547691X.2025.2453156

Bingjun Qian, Jun Hu, Li Dai, Yue Zhou, Haixia Xu

{"title":"Anti-inflammatory effect of Plantago asiatica crude extract in rat gout arthritis model.","authors":"Bingjun Qian, Jun Hu, Li Dai, Yue Zhou, Haixia Xu","doi":"10.1080/1547691X.2025.2453156","DOIUrl":"10.1080/1547691X.2025.2453156","url":null,"abstract":"Plantago asiatica L., a perennial herb in the family Plantaginaceae, has been shown to impart several pharmacologic activities, including anti-oxidative, anti-inflammatory, and diuretic effects. In the study here, the anti-gout(y) arthritis (GA) effects of a crude extract from P. asiatica L. (PAE) were investigated in a rat GA model. For this, PAE was prepared by ethanol extraction and analyzed for phytochemicals by RP-HPLC and Q-TOF-MS. Thereafter, potential therapeutic effects of the PAE were investigated in rats; Wistar rats (male, 8 wk-of-age) were randomly allocated into four groups (n = 9/group) and intra-articularly injected with 3 mg monosodium urate (MSU) in saline solution to establish a GA model. For the study, rats received oral dosings of 0.3 mg colchicine/kg or 1 g PAE/kg (w/w) before and after gout was established. At fixed times after the treatments, assessment of joint swelling ratios and pathological changes in the joints, as well as of select cytokine expression in the blood, was done. RP-HPLC results showed the PAE contained at least 8 'active' ingredients, with plantamajoside, verbascoside, and cymaroside being the most abundant. In comparison to in control rats, MSU induced joint space narrowing, ankle joint swelling, and increased levels of pro-inflammatory interleukin (IL)-1β, IL-17a, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ, and reductions in anti-inflammatory IL-10 in the blood. PAE treatment significantly reversed patho- genic joint space narrowing and swelling, reversed the MSU-induced changes in inflammatory factors, and in general imparted effects very similar to those seen with colchicine (COL; known non-steroidal anti-inflammatory drug for clinical treatment of GA). Collectively, these findings provide experimental evidence supporting the potential applicability of PAE to treat gouty arthritis.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"22 1","pages":"2453156"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A four-week study on the toxicity of repeated intramuscular administration of plant-based BA-CoV2-0301 vaccine against SARS-CoV-2 in Sprague-Dawley rats. 在Sprague-Dawley大鼠中反复肌注抗SARS-CoV-2植物基BA-CoV2-0301疫苗为期四周的毒性研究

IF 2.4 4区医学

Journal of Immunotoxicology Pub Date : 2025-12-01 Epub Date: 2025-05-14 DOI: 10.1080/1547691X.2025.2504401

Sang-Jin Park, Seonghyeon Kim, Eun-Young Gu, Heejin Park, Wan-Jung Im, Seung Eui Min, Bo-Hwa Choi, NamHyung Kim, Min Seong Jang, Yoongi Kim, Kang-Hyun Han, Kyong-Cheol Ko, Eui-Ju Hong, Yong-Bum Kim

{"title":"A four-week study on the toxicity of repeated intramuscular administration of plant-based BA-CoV2-0301 vaccine against SARS-CoV-2 in Sprague-Dawley rats.","authors":"Sang-Jin Park, Seonghyeon Kim, Eun-Young Gu, Heejin Park, Wan-Jung Im, Seung Eui Min, Bo-Hwa Choi, NamHyung Kim, Min Seong Jang, Yoongi Kim, Kang-Hyun Han, Kyong-Cheol Ko, Eui-Ju Hong, Yong-Bum Kim","doi":"10.1080/1547691X.2025.2504401","DOIUrl":"10.1080/1547691X.2025.2504401","url":null,"abstract":"In December 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China, leading to the global Coronavirus Disease pandemic. The rapid spread of SARS-CoV-2 highlighted the urgent need for effective vaccines. However, the high cost, cold storage requirements, and scalability challenges associated with mRNA vaccines have necessitated alternative vaccine technologies. In the study, the safety of a plant-based vaccine was evaluated. The vaccine, an emulsion of the SARS-CoV-2 S1 antigen and a synthetic TLR4 agonist produced and purified from Nicotiana benthamiana, was administered to Sprague-Dawley rats three times over 4 wk. Mortality, clinical signs, body weight, food consumption, vision, urinalysis, gross findings, organ weight, hematology, serum biochemistry, histopathology, and immunogenicity were evaluated. The results showed that antibodies were efficiently produced and maintained for one month following vaccination with the plant-derived receptor-binding domain (RBD) antigen of COVID-19. Furthermore, the rats showed no toxicological symptoms, with reversible changes at the injection site and minor histological alterations in the spinal cord and bone marrow, typical of vaccine responses. The plant-derived SARS-CoV-2 vaccine appears safe following repeated administration over 4 wk and represents a promising alternative for potential use in human clinical trials and clinical applications.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"22 1","pages":"2504401"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of efgartigimod treatment on humoral and cellular immune responses: analysis of T-cell-dependent antibody response in cynomolgus monkeys. 费加替莫对食蟹猴体液和细胞免疫反应的影响：t细胞依赖性抗体反应的分析。

IF 2.4 4区医学

Journal of Immunotoxicology Pub Date : 2025-12-01 Epub Date: 2025-02-13 DOI: 10.1080/1547691X.2025.2459934

Ornella Binazon, Mario Cocco, Daniel Thwaites, Christopher Cooper, Mahan Moshir, Peter Vanhoenacker, Dieter Defever, Ariëlla Van de Sompel, Sophie Steeland, Gwenda Pynaert, Peter Ulrichts, Judith Baumeister

{"title":"Effects of efgartigimod treatment on humoral and cellular immune responses: analysis of T-cell-dependent antibody response in cynomolgus monkeys.","authors":"Ornella Binazon, Mario Cocco, Daniel Thwaites, Christopher Cooper, Mahan Moshir, Peter Vanhoenacker, Dieter Defever, Ariëlla Van de Sompel, Sophie Steeland, Gwenda Pynaert, Peter Ulrichts, Judith Baumeister","doi":"10.1080/1547691X.2025.2459934","DOIUrl":"10.1080/1547691X.2025.2459934","url":null,"abstract":"Efgartigimod is a human IgG1 antibody Fc fragment that reduces IgG levels through neonatal Fc receptor blockade. This study evaluated whether efgartigimod affects the generation of T-cell-dependent antibodies and cellular immune responses to keyhole limpet hemocyanin (KLH) immunization in non-human primates. Cynomolgus monkeys received efgartigimod or vehicle control intravenously for 11 wk, followed by a recovery phase. KLH challenges occurred during both the dosing phase and the recovery phase. No statistically significant differences emerged in anti-KLH IgM levels between the efgartigimod and control groups. Likewise, comparable KLH-specific T cell responses were observed between groups. Anti-KLH IgG titers were lower in efgartigimod-treated animals compared with controls only after the first boost of KLH, coinciding with decreases in total IgG titers in efgartigimod-treated animals, and returned to baseline levels by the end of the recovery phase. Taken together, these results indicate that efgartigimod does not suppress T-cell-dependent antibody responses or antibody class-switching. The findings of this study are consistent with efgartigimod's pharmacological mechanism of action and suggest that efgartigimod does not impair the generation of effective immune responses.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"22 1","pages":"2459934"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction. 修正。

IF 2.4 4区医学

Journal of Immunotoxicology Pub Date : 2025-12-01 Epub Date: 2025-04-11 DOI: 10.1080/1547691X.2025.2483130

引用次数: 0

Inflammatory markers in prostate cancer: potential roles in risk stratification and immune profiling. 前列腺癌的炎症标志物：在风险分层和免疫分析中的潜在作用。

IF 2.4 4区医学

Journal of Immunotoxicology Pub Date : 2025-12-01 Epub Date: 2025-04-28 DOI: 10.1080/1547691X.2025.2497776

Edgaras Burzinskis, Ieva Janulaityte, Mindaugas Jievaltas, Darijus Skaudickas, Guoda Burzinskiene, Edvinas Dainius, Albinas Naudziunas, Astra Vitkauskiene

{"title":"Inflammatory markers in prostate cancer: potential roles in risk stratification and immune profiling.","authors":"Edgaras Burzinskis, Ieva Janulaityte, Mindaugas Jievaltas, Darijus Skaudickas, Guoda Burzinskiene, Edvinas Dainius, Albinas Naudziunas, Astra Vitkauskiene","doi":"10.1080/1547691X.2025.2497776","DOIUrl":"https://doi.org/10.1080/1547691X.2025.2497776","url":null,"abstract":"Inflammation plays a critical role in prostate cancer (PCa) pathophysiology, yet the diagnostic value of specific inflammatory markers remains unclear. This study evaluates the association between circulating and tissue inflammatory markers with PCa presence and their potential as biomarkers for risk stratification. This prospective study analyzed serum and prostate biopsy samples from 60 patients with PCa and 22 cancer-free controls. Concentrations of inflammatory markers, including IL-2, IL-4, IL-10, IL-13, IL-33, Oncostatin M, TNFα, PDGF-BB, and TREM-1, were measured using Luminex technology. Statistical analyses included the Mann-Whitney test, logistic regression, and ROC curve analysis to assess differences and diagnostic performance. PCa patients exhibited significantly higher serum levels of IL-2 (p = 0.001), IL-10 (p < 0.001), IL-33 (p < 0.001), Oncostatin M (p = 0.018), and TNFα (p = 0.017) compared to controls. In contrast, biopsy tissue levels of IL-4 (p < 0.001), IL-10 (p < 0.001), IL-13 (p = 0.004), Oncostatin M (p = 0.012), PDGF-BB (p = 0.039), and TREM-1 (p = 0.013) were significantly lower in PCa patients, suggesting an inverse association. IL-10 (inverse) and IL-4 (inverse) in biopsy tissue showed high specificity in ROC analysis (AUC = 0.788 and 0.804, respectively), while IL-2 and IL-33 in serum were positively associated with PCa risk. This study suggests that IL-4, IL-10, and IL-13 in biopsy tissue may serve as biomarkers of a protective effect, while elevated IL-2 and IL-33 in serum are associated with an increased risk of PCa. These findings highlight the potential of inflammatory markers in PCa risk stratification, warranting further investigation in larger cohorts.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"22 1","pages":"2497776"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Generation of cynomolgus monkey capsid-specific positive control cells for IFNγ ELISpot assays for adeno-associated gene therapy applications. 产生食蟹猴衣壳特异性阳性对照细胞用于IFNγ ELISpot检测，用于腺相关基因治疗应用。

IF 2.4 4区医学

Journal of Immunotoxicology Pub Date : 2025-12-01 Epub Date: 2025-02-13 DOI: 10.1080/1547691X.2025.2459931

Sandra Casinghino, Karrie Tartaro, Jessica Anderson, Ravindra C Kodihalli, Sophia G Lee, Jessie Qian, Patricia A Schneider, Richard Virgen-Slane, Laurence O Whiteley, Thomas A Lanz

{"title":"Generation of cynomolgus monkey capsid-specific positive control cells for IFNγ ELISpot assays for adeno-associated gene therapy applications.","authors":"Sandra Casinghino, Karrie Tartaro, Jessica Anderson, Ravindra C Kodihalli, Sophia G Lee, Jessie Qian, Patricia A Schneider, Richard Virgen-Slane, Laurence O Whiteley, Thomas A Lanz","doi":"10.1080/1547691X.2025.2459931","DOIUrl":"10.1080/1547691X.2025.2459931","url":null,"abstract":"Cell-mediated immune (CMI) responses to adeno-associated virus (AAV) can lead to tissue damage and loss of therapeutic transgene expression. Identifying robust biomarkers and mechanisms of CMI can aid clinical practice and advancement of AAV gene therapies. The present work evaluated peripheral blood mononuclear cells (PBMC) from non-human primates (NHP) before and after immunization with adenovirus 5 encoding AAV9 capsid antigen. PBMC were stimulated ex vivo with AAV9 capsid peptides to evaluate CMI responses by interferon (IFN)-γ ELISpot, intracellular cytokines/activation markers, secreted cytokines, and RNAseq. AAV peptide stimulation produced a robust IFNγ ELISpot 11 days after immunization and ≈ 4 years after cryopreservation. Flow cytometry revealed increased IFNγ, interleukin (IL)-2, or tumor necrosis factor (TNF)-positive T-cells. Increases in secreted CXCR3 ligands (IP-10, I-TAC) were detected. Robust changes and correlations to ELISpot responses were revealed by RNAseq, including IFNγ, IP-10, and I-TAC, many downstream transcripts, and several IFN-independent pathways. These data from AAV-immunized NHP identify biomarkers that could serve as robust and sensitive supplements/alternatives to ELISpot for early detection of CMI responses. Assessment of these biomarkers in non-clinical and clinical studies is a critical next step to determine the translation of this work to administration of a therapeutic AAV vector.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"22 1","pages":"2459931"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0