Journal of Immunotoxicology最新文献

{"title":"Summary of a workshop on preclinical and translational safety assessment of CD3 bispecifics.","authors":"Cris Kamperschroer,&nbsp;Jacintha Shenton,&nbsp;Hervé Lebrec,&nbsp;John K Leighton,&nbsp;Paul A Moore,&nbsp;Oliver Thomas","doi":"10.1080/1547691X.2020.1729902","DOIUrl":"https://doi.org/10.1080/1547691X.2020.1729902","url":null,"abstract":"<p><p>Currently, there is a multitude of CD3 bispecifics with different molecular designs and binding properties in preclinical and clinical development for the treatment of liquid or solid tumors. The key safety concerns with CD3 bispecifics are excessive release of cytokines, which may translate to potentially life-threating cytokine release syndrome (CRS), target organ toxicity due to redirection of T-cells to normal tissues expressing the tumor-associated antigen (TAA) (off-tumor/on-target cytotoxicity), and, in some instances, neurotoxicity. Another key challenge is to arrive at a safe clinical starting dose and an efficient escalating strategy that allows patients in early dose cohorts the potential for clinical benefit in Phase 1 trials. To expand the therapeutic index and bring more treatment options to patients, there are intense efforts to overcome these challenges through improvements in molecular design, preclinical safety assessment strategies, and clinical management practices. A recent workshop at the U.S. Food and Drug Administration (FDA) with industry, academic, and regulatory agency representation was held to discuss the challenges and explore where such improvements to the development of CD3 bispecifics can be implemented. Here, the content of the presentations and the discussion that occurred during this workshop are summarized.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"67-85"},"PeriodicalIF":3.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2020.1729902","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37678768","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}

{"title":"KMRC011, an agonist of toll-like receptor 5, mitigates irradiation-induced tissue damage and mortality in cynomolgus monkeys.","authors":"Hong-Soo Lee,&nbsp;Doo-Wan Cho,&nbsp;Ji-Seok Han,&nbsp;Su-Cheol Han,&nbsp;Sang Keun Woo,&nbsp;Soo-Youn Jun,&nbsp;Woo-Jong Lee,&nbsp;Susie Yoon,&nbsp;Son-Il Pak,&nbsp;Sang-Jin Lee,&nbsp;Eunsol Seong,&nbsp;Eun-Jung Park","doi":"10.1080/1547691X.2019.1699617","DOIUrl":"https://doi.org/10.1080/1547691X.2019.1699617","url":null,"abstract":"<p><p>In the study here, the potential applicability of KMRC011 - an agonist of toll-like receptor-5 - as a countermeasure for radiation toxicities was evaluated. Following a single 5.5 Gy total body irradiation (TBI, surface absorbed dose = 7 Gy) of Co⁶⁰ γ-rays, mortality rates and degrees of pathological lesions that developed over 80 days were compared in monkeys that received TBI only and a group that was injected once with KMRC011 (10 μg/kg) after TBI. Compared to the TBI-only hosts (80%), the death rate was significantly improved by the use of KMRC011 (40%), all deaths in both groups occurred in the period from Days 19-24 post-TBI. Further analysis of monkeys that survived until the end of the experiment showed that AST and ALT levels were elevated only in the TBI group, and that radiation-induced tissue damage was alleviated by the KMRC011 injection. Additionally, expression of cell death-related proteins was lower in tissues from the KMRC011-treated hosts than in those in the TBI-only group. Other measured parameters, including body weight, food uptake, and hematological values did not significantly differ between the two groups over the entire period. The results of this study, thus demonstrate that KMRC011 could potentially be used as a medical countermeasure for the treatment of acute radiation exposure.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"31-42"},"PeriodicalIF":3.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2019.1699617","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37607108","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}

{"title":"Immunostimulatory effects on THP-1 cells by peptide or protein pharmaceuticals associated with injection site reactions.","authors":"Eri Hamamura-Yasuno,&nbsp;Tetsuo Aida,&nbsp;Yoshimi Tsuchiya,&nbsp;Kazuhiko Mori","doi":"10.1080/1547691X.2020.1727071","DOIUrl":"https://doi.org/10.1080/1547691X.2020.1727071","url":null,"abstract":"<p><p>Injection site reaction (ISR) is a common side-effect associated with the use of peptide or protein pharmaceuticals. These types of pharmaceuticals-induced activation of antigen-presenting cells is assumed to be a key step in the pathogenesis of immune-mediated ISR. The present study was designed to evaluate the immunostimulatory properties of peptide or protein pharmaceuticals using human monocytic THP-1 cells. Here, THP-1 cells, with or without phorbol-12-myristate-13-acetate (PMA) pretreatment, were exposed to enfuvirtide and glatiramer acetate (positive controls) or evolocumab (negative control) for 6 or 24 h. PMA treatment differentiated non-adherent monocytic THP-1 (nTHP-1) cells into adherent macrophagic THP-1 (pTHP-1) cells that highly express CD11b and CD36. Enfuvirtide increased the release of cytokines, e.g. TNFα, MIP-1β, and MCP-1, and expression of CD86 and CD54 on nTHP-1 cells at 24 h. Similar immunostimulatory properties of glatiramer acetate were observed both in the nTHP-1 and pTHP-1 cells at 6 h, but the responses were very weak in the pTHP-1 cells. Evolocumab did not affect cytokine secretion or cell surface marker expression in either cell type. Taken together, these <i>in vitro</i> THP-1 cell assays revealed the immunostimulatory properties of enfuvirtide and glatiramer acetate. This assay platform thus could serve as a powerful tool in evaluating potential immune-related ISR risks of peptide or protein pharmaceuticals in humans.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"59-66"},"PeriodicalIF":3.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2020.1727071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37670523","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}

{"title":"Cross-company evaluation of the human lymphocyte activation assay.","authors":"Mark Collinge,&nbsp;Patricia Schneider,&nbsp;Dingzhou Li,&nbsp;Stanley Parish,&nbsp;Carolyne Dumont,&nbsp;Wendy Freebern,&nbsp;Joseph Ghanime,&nbsp;Fanny Guimont-Derochers,&nbsp;Anja Langenkamp,&nbsp;Jose Lebron,&nbsp;Nianyu Li,&nbsp;Celine Marban,&nbsp;Lisa Plitnick,&nbsp;Jennifer Wheeler","doi":"10.1080/1547691X.2020.1725694","DOIUrl":"https://doi.org/10.1080/1547691X.2020.1725694","url":null,"abstract":"<p><p>Nonclinical immunotoxicity evaluation is an important component of safety assessment for pharmaceuticals. One <i>in vitro</i> assay that can be applied in a weight of evidence assessment is the human lymphocyte activation (HuLA) assay, an antigen recall assay, similar in many respects to the <i>in vivo</i> T-cell-dependent antibody response (TDAR) in that cooperation of multiple immune cell types are needed to produce responses. This assay uses human cells and is more amenable than the TDAR to compound ranking and mechanistic studies. The HuLA assay requires less time and drug than TDAR assays, uses a relevant antigen (influenza), reflects a human immune response, and applies principles of the 3Rs to non-clinical safety assessment. Peripheral blood mononuclear cells (PBMC) from flu-immunized donors are re-stimulated with flu-vaccine in the presence of test articles, and proliferation is measured. Published data demonstrate the applicability of the HuLA assay, but it has not been evaluated for reproducibility across testing sites. To evaluate assay reproducibility, scientists from a consortium of institutions conducted the assay in parallel, using a common pool of donor PBMC, influenza vaccine, and known immunosuppressant compounds (cyclosporine A and mycophenolic acid). The HuLA assay was highly reproducible in identification of inhibition of antigen-specific responses, and there was significant agreement across testing sites in the half maximal inhibitory concentration (IC₅₀) values. Intra-site variability was the largest contributor to the variability observed within the assay. The HuLA assay was demonstrated to be ideally suited to comparing multiple compounds (i.e. compound ranking or benchmarking) within the same assay. Overall, the data reported herein support the HuLA assay as a useful tool in mechanistic evaluations of antigen-specific immune responses.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"51-58"},"PeriodicalIF":3.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2020.1725694","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37699770","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}

{"title":"Local inflammatory marker production in Lithuanian patients with chronic rhinosinusitis with nasal polyps.","authors":"Justinas Vaitkus,&nbsp;Astra Vitkauskiene,&nbsp;Vilte Matuseviciute,&nbsp;Albinas Naudziunas,&nbsp;Nora Siupsinskiene,&nbsp;Saulius Vaitkus","doi":"10.1080/1547691X.2020.1850938","DOIUrl":"https://doi.org/10.1080/1547691X.2020.1850938","url":null,"abstract":"<p><p>There are two clinical subtypes of chronic rhinosinusitis (CRS): chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP). The aim of the study here was to determine the levels of invasive inflammatory markers in nasal mucosa samples taken from CRSwNP patients during the surgery and to identify markers that could serve as targets for potential clinical and therapeutic interventions. The study was carried out in 59 patients with proven CRSwNP and a control group consisting of 52 healthy individuals. Concentrations of the inflammatory markers of interest were determined using a LuminexR Assay multiplex kit. The data obtained indicated that levels of inflammatory cytokines interleukin (IL)-2, -4, -5, -7, -12, -17 and -22 were all significantly higher in the nasal polyps (NP) than those in the mucosa of control participants. No differences were seen between the study groups for IL -6, -10, -13, -21 and interferon (IFN)-γ. OR (Odds Ratio) analyses confirmed that elevations in mucosal levels of IL-2, -4, -5, -7, -12, -17, and -22 were likely immune markers of CRSwNP. In conclusion, the present study demonstrated that IL-2, -4, -12 and -22 may be important in the etiopathogenesis of CRSwNP; as markers, each show moderate sensitivity, but high specificity in the Lithuanian population. IL-17 had good sensitivity, but low specificity in the CRSwNP patients.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"202-206"},"PeriodicalIF":3.3,"publicationDate":"2020-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2020.1850938","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38363160","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}

{"title":"Altered levels of complement components associated with non-immediate drug hypersensitivity reactions","authors":"Feng Wang, Liping Huang, Jun-Hao Yu, D. Zang, Liang-ping Ye, Qi-xing Zhu","doi":"10.1080/1547691x.2019.1695985","DOIUrl":"https://doi.org/10.1080/1547691x.2019.1695985","url":null,"abstract":"Abstract Nonimmediate drug hypersensitivity reactions (niDHRs) range from mild-type maculopapular exanthema (MPE) to severe type Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with unentirely clarified pathogenesis. This study sought to explore whether complement components participated in niDHRs. The participants comprised of three groups as follows: MPE (n = 65), SJS/TEN (n = 13, contains 7 SJS, 2 SJS-TEN overlap and 4 TEN), and equal healthy controls (n = 78). Skin pathological changes were confirmed by hematoxylin and eosin staining. The mRNA and protein levels of complement components were assessed. In the MPE group, there were no alterations in complement components at the protein and mRNA levels found except for a decrease in factor H mRNA. In the SJS/TEN group, up-regulated levels of C3aR and C5aR mRNA and down-regulated factor H mRNA levels in blood were noted. A lower plasma protein level of C3, Factor H and a higher level of C3a, C5, C5a, C5b-9, Factor B (p < 0.05) were found in the SJS/TEN group compared with in the control (p < 0.05). In SJS/TEN skin lesions, indirect immunofluorescence assays showed positive specific staining for C5b-9, but not C3. Both C3aR and C5aR were positive staining in the SJS/TEN samples, while staining for C1q, mannose-binding lectin (MBL), Factor B, and Factor H were only weak or negative. The findings reported here are the first to define the expression profiles/extent of the presence of various complement components at the mRNA and protein levels in niDHRs, especially in SJS/TEN. These altered complement components might, at least in part, be integral to the mechanisms underlying the pathogeneses of SJS and TEN.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"17 1","pages":"1 - 9"},"PeriodicalIF":3.3,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691x.2019.1695985","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47525182","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}

{"title":"Immunotoxicity studies of trans-resveratrol in male B6C3F1/N mice","authors":"Madelyn C. Huang, K. White, S. Elmore, T. Guo, D. Germolec","doi":"10.22427/ntp-data-002-02772-0033-0000-6","DOIUrl":"https://doi.org/10.22427/ntp-data-002-02772-0033-0000-6","url":null,"abstract":"Abstract Resveratrol is a naturally occurring polyphenol that is being investigated to treat and prevent various diseases, both experimentally and in the clinic. Despite increased use and interest in resveratrol due to its immunomodulatory properties, there is a lack of studies evaluating potential toxicities, particularly immunotoxicity, associated with resveratrol use. A previous 2-week study found decreasing thymus weight in male B6C3F1/N mice with increasing exposure to trans-resveratrol. This study is a follow-up on those findings by evaluating immune function. Male adult B6C3F1/N mice were given trans-resveratrol (0, 156, 312, 625, 1250, 2500 mg/kg/day) via oral gavage for 28 days and functional immune tests and histopathology were evaluated. There were no treatment-related effects on body weight during the study. Humoral, cell-mediated, and innate immune function were not altered after 28 days of trans-resveratrol treatment. There were also no changes in organ weight or microscopic alterations in immune organs. Overall, under the conditions of this study, there was no evidence of immunotoxicity or improvements in immune function associated with oral exposure to trans-resveratrol in male mice. Importantly, the immunomodulatory benefits of resveratrol may require a prerequisite level of inflammatory activity and may not be observable in healthy individuals.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"17 1","pages":"194 - 201"},"PeriodicalIF":3.3,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49299556","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}

{"title":"Effects of quercetin on Aroclor 1254-induced expression of CYP₄₅₀ and cytokines in pregnant rats.","authors":"Lina Xu,&nbsp;Xiaojun Guo,&nbsp;Nan Li,&nbsp;Qing Pan,&nbsp;Yu Zhong Ma","doi":"10.1080/1547691X.2019.1604585","DOIUrl":"https://doi.org/10.1080/1547691X.2019.1604585","url":null,"abstract":"<p><p>The present study aimed to investigate the protective effect of quercetin on polychlorinated biphenyls (PCB)-induced liver and embryo damage in pregnant Sprague-Dawley rats. Pregnant rats were divided into five groups, and then were orally gavaged daily with peanut oil (vehicle) or a commercial PCB mixture (Aroclor 1254) - with or without co-treatment with 75, 150, or 300 mg/kg quercetin - on gestation days (GD) 4-7. At GD 9, all rats were euthanized, and their blood, liver, and uterus were collected. Expressions of <i>CYP</i>₄₅₀ mRNA and protein in liver, cytokines (IFNγ, IL-2, IL-4, and IL-6) and IFNγ/IL-4 ratios in liver and sera, liver morphology, and the status of implanted embryos were analyzed. The results showed Aroclor 1254 treatment alone caused hepatic cord damage (i.e. cell disorganization, swelling, decreased cytoplasm, vacuolization), and that quercetin co-treatment appeared to mitigate this damage. Similarly, levels of <i>CYP1A1</i> and <i>CYP2B1</i> mRNA in livers of Aroclor 1254-only-treated rats were significantly higher than those in rats co-treated with quercetin. Hepatic and sera levels of IFNγ, IL-2, IL-6, and IFNγ/IL-4 ratios, and the ratio of delayed-development embryos, all increased in Aroclor 1254-treated rats, but were relatively decreased as a result of quercetin co-treatments. IL-4 levels were decreased by Aroclor 1254 and tended to increase back to normal when quercetin was used. The results indicated that quercetin imparted a protective effect against Aroclor 1254-induced toxicity in pregnant rats, in part, by modulating levels of important pro-inflammatory cytokines and reducing induced CYP1A1 and CYP2B1 expression.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"16 1","pages":"140-148"},"PeriodicalIF":3.3,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2019.1604585","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37132833","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}

{"title":"An ELISA for detection of complement-bound circulating immune complexes in mice.","authors":"Lykke Boysen,&nbsp;Brian Lauritzen,&nbsp;Birgitte Martine Viuff,&nbsp;Jens Lykkesfeldt,&nbsp;Lone Hummelshøj Landsy","doi":"10.1080/1547691X.2019.1599471","DOIUrl":"https://doi.org/10.1080/1547691X.2019.1599471","url":null,"abstract":"<p><p>Measurements of complement-bound circulating immune complexes (cCICs) in pre-clinical studies may provide important information about the etiology of certain pathology findings suggestive of being immune complex mediated. This article describes the development and qualification of a universal methodology to measure cCIC in mice after dosing with species foreign proteins. The assay is a sandwich enzyme-linked immunosorbent assay - exclusively based on commercially available reagents - that could detect mouse IgG bound to complement C3 independent of the test-substance present in the plasma sample. Heat-aggregated serum was used as positive control. The assay was qualified by assessment of acceptance criteria, stability of positive control, precision, and specificity. Finally, the performance of the assay was tested using plasma from mice administered either of three different proteins, i.e bovine serum albumin (BSA), a fully human monoclonal antibody, and a humanized monoclonal antibody.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"16 1","pages":"82-86"},"PeriodicalIF":3.3,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2019.1599471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37391851","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}

{"title":"<i>In vitro</i> human helper T-cell assay to screen antibody drug candidates for immunogenicity.","authors":"Shunsuke Ito,&nbsp;Tatsuya Ikuno,&nbsp;Masayuki Mishima,&nbsp;Mariko Yano,&nbsp;Toshiko Hara,&nbsp;Taichi Kuramochi,&nbsp;Zenjiro Sampei,&nbsp;Tetsuya Wakabayashi,&nbsp;Mitsuyasu Tabo,&nbsp;Shuichi Chiba,&nbsp;Chiyomi Kubo","doi":"10.1080/1547691X.2019.1604586","DOIUrl":"https://doi.org/10.1080/1547691X.2019.1604586","url":null,"abstract":"<p><p>Monoclonal antibody (mAb) drugs offer a number of valuable treatments. Many newly developed mAb drugs include artificial modification of amino acid sequences from human origin, which may cause higher immunogenicity to induce anti-drug antibodies (ADA). If the immunogenicity of a new candidate can be understood in the nonclinical phase, clinical studies will be safer and the success rate of development improved. Empirically, <i>in vitro</i> immunogenicity assays with human cells have proved to be sufficiently sensitive to nonhuman proteins, but not to human/humanized mAb. To detect the weaker immunogenicity of human-based mAb, a more sensitive biomarker for <i>in vitro</i> assays is needed. The <i>in vitro</i> study here developed a proliferation assay (T_H cell assay) using flow cytometry analysis that can detect a slight increase in proliferating T_H cells. Samples from 218 donors treated with a low-immunogenic drug (etanercept) were measured to determine a positive threshold level. With this threshold, positive donor percentages among PBMC after treatment with higher-immunogenicity mAb drugs were noted, that is, 39.5% with humanized anti-human A33 antibody (hA33), 27.3% with abciximab, 25.9% with adalimumab, and 14.8% with infliximab. Biotherapeutics with low immunogenicity yielded values of 0% for basiliximab and 3.7% for etanercept. These data showed a good comparability with previously reported incidences of clinical ADA with the evaluated drugs. Calculations based on the data here showed that a T_H cell assay with 40 donors could provide statistically significant differences when comparing low- (etanercept) versus highly immunogenic mAb (except for infliximab). Based on the outcomes here, for screening purposes, a practical cutoff point of 3/20 positives with 20 donors was proposed to alert immunogenicity of mAb drug candidates.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"125-132"},"PeriodicalIF":3.3,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2019.1604586","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40451848","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}