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Bispecific T-cell engagers for the recruitment of T cells in solid tumors: a literature review. 用于实体瘤 T 细胞招募的双特异性 T 细胞吸引剂:文献综述。
IF 4.1
Immunotherapy advances Pub Date : 2025-01-27 eCollection Date: 2025-01-01 DOI: 10.1093/immadv/ltae005
Laura Dewaele, Ricardo A Fernandes
{"title":"Bispecific T-cell engagers for the recruitment of T cells in solid tumors: a literature review.","authors":"Laura Dewaele, Ricardo A Fernandes","doi":"10.1093/immadv/ltae005","DOIUrl":"10.1093/immadv/ltae005","url":null,"abstract":"<p><p>In the past decade, T-cell-based immunotherapies have grown to become some of the most promising treatments for cancer. Following the success of immune checkpoint inhibitors, other T-cell-based therapies emerged including CAR-T cells and bispecific T-cell engagers (BiTEs). BiTEs have the unique ability to crosslink T cells and tumor cells independently of major histocompatibility complex (MHC) restriction. They do not rely on TCR specificity or the CD4+/CD8+ costimulatory molecules, overcoming tumor MHC downregulation and low-affinity TCR binding. However, like many other immunotherapies, BiTEs have shown limited success beyond the treatment of hematological malignancies. BiTEs for the treatment of solid tumors still face challenges. Studies in gastrointestinal tumors have revealed Fc toxicity, short half-lives, and immunotoxicity, leading to Fc-silenced half-life extended BiTEs with humanized single-chain variable fragments. Studies in prostate tumors, lung tumors, and malignant gliomas have identified promising targets in PSMA, DLL3, and EGFRvIII, respectively, but also highlighted the problems of on-target off-tumor and BiTE-specific toxicities and inaccessible or immunosuppressive tumor microenvironments. Ongoing research to overcome these limitations remains an interesting field to follow, as BiTEs have the potential to be a powerful tool, especially when used in combination with other immunotherapies.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltae005"},"PeriodicalIF":4.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Delivery of IL-12 by neoantigen-reactive T cells promotes antitumor immunity in murine osteosarcoma mode. 新抗原反应性T细胞传递IL-12促进小鼠骨肉瘤模式的抗肿瘤免疫。
IF 4.1
Immunotherapy advances Pub Date : 2024-11-28 eCollection Date: 2025-01-01 DOI: 10.1093/immadv/ltae010
Cong Tian, Xingxing Sun, Hongling Zhu, Meixiang Zhou, Qingyu Chen, Daliu Min, Yan Huang, Kun Han
{"title":"Delivery of IL-12 by neoantigen-reactive T cells promotes antitumor immunity in murine osteosarcoma mode.","authors":"Cong Tian, Xingxing Sun, Hongling Zhu, Meixiang Zhou, Qingyu Chen, Daliu Min, Yan Huang, Kun Han","doi":"10.1093/immadv/ltae010","DOIUrl":"10.1093/immadv/ltae010","url":null,"abstract":"<p><strong>Purpose: </strong>Despite the proven clinical benefits of cytokine therapy in cancer treatment, systemic administration of cytokines such as IL-12 is constrained by dose-limiting toxicities and short half-lives. To address these challenges, we explored a localized cytokine delivery strategy using engineered neoantigen-reactive T (NRT) cells as carriers in a murine model of osteosarcoma.</p><p><strong>Materials and methods: </strong>We used a neoantigen from K7M2 osteosarcoma cells to retrovirally transduce NRT cells to express an inducible form of IL-12. We evaluated the engineered NRT cells' antitumor activity and the production of IL-12 and IFN-γ upon in vitro co-culture with tumor cells. We systemically administered NRT-IL-12 cells in a mouse model of osteosarcoma to assess their impact on tumor growth and survival.</p><p><strong>Results: </strong><i>In vitro</i> assays demonstrated that the engineered NRT cells exhibited enhanced antitumor activity and produced elevated levels of IL-12 and IFN-γ. In the mouse model of osteosarcoma, systemic administration of NRT-IL-12 cells resulted in a significant reduction in tumor growth and an increase in survival rates compared to the administration of control NRT cells. Further analysis revealed that NRT-IL-12 cells induced a profound increase in CD8+ T-cell infiltration and a decrease in Treg cells within the tumor microenvironment.</p><p><strong>Conclusion: </strong>Our study presents a novel and efficacious strategy for osteosarcoma immunotherapy by harnessing NRT cells as targeted cytokine delivery vehicles.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"5 1","pages":"ltae010"},"PeriodicalIF":4.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Systematic review and meta-analysis of COVID-19 mRNA vaccine effectiveness against hospitalizations in adults. COVID-19 mRNA疫苗对成人住院治疗有效性的系统评价和荟萃分析
IF 4.1
Immunotherapy advances Pub Date : 2024-11-27 eCollection Date: 2024-01-01 DOI: 10.1093/immadv/ltae011
Bill Kang-Fai Wong, Neil A Mabbott
{"title":"Systematic review and meta-analysis of COVID-19 mRNA vaccine effectiveness against hospitalizations in adults.","authors":"Bill Kang-Fai Wong, Neil A Mabbott","doi":"10.1093/immadv/ltae011","DOIUrl":"10.1093/immadv/ltae011","url":null,"abstract":"<p><strong>Background: </strong>During the coronavirus disease 2019 (COVID-19) pandemic, Pfizer/BioNTech BNT162b2, and Moderna mRNA-1273 vaccines were central to the global pandemic control measures.</p><p><strong>Methods: </strong>Here, we conducted a systematic review and meta-analysis to evaluate their real-world vaccine effectiveness (VE). Our study focussed on those that reported the efficacy of these vaccines against COVID-19 hospitalization. Hospitalization was chosen as the primary outcome as it directly reflects the ability of the vaccine to prevent severe disease. A literature search was undertaken using Medline and Embase on 25 February 2024. From this, 50 studies out of 18,347 articles were included for further analysis.</p><p><strong>Results: </strong>High VE against hospitalization was reported for both the BNT162b2 and mRNA-1273 COVID-19 vaccines when used either as a primary vaccination series (2-dose) or following an additional booster dose (3-dose). Meta-analysis indicated that the pooled VE estimates for each of these vaccination protocols ranged from 84% to 86%, suggesting strong protectiveness. Our data also imply that booster doses can restore waning effectiveness, with no significant differences observed in VE between the 2-dose and 3-dose protocols. However, subgroup analysis revealed an association between the presence of the Omicron variant and a drop in VE, indicating that future emerging SARS-CoV-2 virus variants could similarly affect VE.</p><p><strong>Conclusions: </strong>Our review underscores the importance of ongoing research to ensure vaccine strategies remain effective against evolving variants. Our study also identified the need for expanding data collection to include underrepresented populations.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"4 1","pages":"ltae011"},"PeriodicalIF":4.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hyperactivation of the PI3K pathway in inborn errors of immunity: current understanding and therapeutic perspectives. 先天性免疫错误中PI3K通路的过度激活:目前的理解和治疗观点。
IF 4.1
Immunotherapy advances Pub Date : 2024-11-07 eCollection Date: 2024-01-01 DOI: 10.1093/immadv/ltae009
Hanna IJspeert, Virgil A S H Dalm, Menno C van Zelm, Emily S J Edwards
{"title":"Hyperactivation of the PI3K pathway in inborn errors of immunity: current understanding and therapeutic perspectives.","authors":"Hanna IJspeert, Virgil A S H Dalm, Menno C van Zelm, Emily S J Edwards","doi":"10.1093/immadv/ltae009","DOIUrl":"10.1093/immadv/ltae009","url":null,"abstract":"<p><p>The phosphoinositide-3-kinase (PI3K) pathway function is crucial to the normal development, differentiation, and function of immune cells including B, T, and NK cells. Following the description of two cohorts of patients with an inboirn error of immunity (also known as primary immunodeficiency) with gain-of-function variants in the <i>PIK3CD</i> gene a decade ago, the disease entity activated PI3K delta syndrome (APDS) was named. Since then, many more patients with <i>PIK3CD</i> variants have been described, and loss-of-function variants in <i>PIK3R1</i> and <i>PTEN</i> have also been linked to APDS. Importantly, the availability of small molecules that inhibit the PI3K pathway has enabled targeted treatment of APDS patients. In this review, we define (i) the PI3K pathway and its role in inborn errors of immunity; (ii) the clinical and immunological presentation of APDS1 (<i>PIK3CD</i> GOF), APDS2 (<i>PIK3R1</i> LOF), and related disorders; (iii) Diagnostic approaches to identify and functionally validate the genetic causes of disease; (iv) therapeutic interventions to target PI3K hyperactivation; and finally (v) current challenges and future perspectives that require attention for the optimal treatment of patients with APDS and APDS-L diseases.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"4 1","pages":"ltae009"},"PeriodicalIF":4.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High-affinity T cell receptor ImmTAC® bispecific efficiently redirects T cells to kill tumor cells expressing the cancer-testis antigen PRAME. 高亲和T细胞受体ImmTAC®双特异性有效地重定向T细胞杀死表达癌睾丸抗原PRAME的肿瘤细胞。
IF 4.1
Immunotherapy advances Pub Date : 2024-11-02 eCollection Date: 2024-01-01 DOI: 10.1093/immadv/ltae008
Ana R Ribeiro, Camille Britton-Rivet, Laura Collins, Ricardo J Carreira, Sylvie Moureau, Adel Benlahrech, Sarah Stanhope, Stephen Harper, Nathaniel Liddy, Tara M Mahon, Kristina Petrovic, Mark Fife, David Depoil, Philip Addis, Nicole Bedke, Lucie Bouard, Ronan O'Dwyer, Duncan Gascoyne, Koustubh Ranade
{"title":"High-affinity T cell receptor ImmTAC® bispecific efficiently redirects T cells to kill tumor cells expressing the cancer-testis antigen PRAME.","authors":"Ana R Ribeiro, Camille Britton-Rivet, Laura Collins, Ricardo J Carreira, Sylvie Moureau, Adel Benlahrech, Sarah Stanhope, Stephen Harper, Nathaniel Liddy, Tara M Mahon, Kristina Petrovic, Mark Fife, David Depoil, Philip Addis, Nicole Bedke, Lucie Bouard, Ronan O'Dwyer, Duncan Gascoyne, Koustubh Ranade","doi":"10.1093/immadv/ltae008","DOIUrl":"10.1093/immadv/ltae008","url":null,"abstract":"<p><strong>Background: </strong>PRAME (<i>Pr</i>eferentially expressed <i>A</i>ntigen in <i>Me</i>lanoma) is a cancer-testis antigen expressed in several tumor indications, representing an attractive anticancer target. However, its intracellular location limits targeting by traditional methods. PRAME peptides are presented on the surface of tumor cells by human leukocyte antigen (HLA) molecules, indicating that a T cell receptor (TCR)-based strategy that redirects T cells to kill PRAME<sup>+</sup> tumors could be a novel immunotherapeutic option. We confirm that PRAME protein is expressed in cutaneous melanoma, including rare subtypes with limited treatment options, as well as primary and metastatic lung, breast, endometrial, and ovarian tumors. Furthermore, PRAME is expressed homogeneously across tumors with distinct oncogenic mutations, mutation burden, PD-L1 expression, immune infiltration, and features of immune checkpoint resistance. Immunopeptidomic analysis of primary tumors detected HLA class I-restricted PRAME peptides.</p><p><strong>Methods: </strong>A TCR recognizing PRAME peptide SLLQHLIGL was engineered to high affinity and fused to a CD3 engaging domain to create a TCRxCD3 bispecific molecule (<i>I</i>mmune-<i>m</i>obilizing <i>m</i>onoclonal TCR <i>A</i>gainst <i>C</i>ancer, ImmTAC®) with the ability to redirect polyclonal T cells to efficiently kill PRAME<sup>+</sup> cells.</p><p><strong>Rs: </strong>The degree of T cell activation was positively correlated with peptide-HLA abundance, with as few as 10 epitopes per cell sufficient for target cell killing. Impaired ImmTAC®-redirected cytotoxicity of exhausted T cells was rescued using an anti-PD-1 antibody, supporting the use of a combination strategy to treat tumors with active PDL1-PD1 axes.</p><p><strong>Conclusions: </strong>Our data demonstrate selective and efficient T cell activation and killing by a PRAME-directed TCRxCD3 bispecific, supporting further investigation in multiple cancer indications.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"4 1","pages":"ltae008"},"PeriodicalIF":4.1,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A rapid method to assess the in vivo multi-functionality of adoptively transferred engineered TCR T cells. 用于评估经收养转移的工程化 TCR T 细胞体内多功能性的快速方法。
IF 4.1
Immunotherapy advances Pub Date : 2024-09-18 eCollection Date: 2024-01-01 DOI: 10.1093/immadv/ltae007
Anthony T Tan, Shou Kit Hang, Nicole Tan, Thinesh L Krishnamoorthy, Wan Cheng Chow, Regina Wanju Wong, Lu-En Wai, Antonio Bertoletti
{"title":"A rapid method to assess the <i>in vivo</i> multi-functionality of adoptively transferred engineered TCR T cells.","authors":"Anthony T Tan, Shou Kit Hang, Nicole Tan, Thinesh L Krishnamoorthy, Wan Cheng Chow, Regina Wanju Wong, Lu-En Wai, Antonio Bertoletti","doi":"10.1093/immadv/ltae007","DOIUrl":"10.1093/immadv/ltae007","url":null,"abstract":"<p><strong>Introduction: </strong>The clinical efficacy of chimeric antigen and T cell receptor (TCR) T cell immunotherapies is attributed to their ability to proliferate and persist <i>in vivo</i>. Since the interaction of the engineered T cells with the targeted tumour or its environment might suppress their function, their functionality should be characterized not only before but also after adoptive transfer.</p><p><strong>Materials and methods: </strong>We sought to achieve this by adapting a recently developed Severe acute respiratory syndrome <i>coronavirus 2</i> (SARS-CoV-2) rapid whole blood T cell assay to stimulate engineered TCR T cells in small volumes of whole blood (<1 ml) without <i>in vitro</i> cellular purification. As a proof-of-concept, we used this method to longitudinally study two patients with primary Hepatitis B Virus (HBV)-related hepatocellular carcinoma who received multiple dose-escalating infusions of transiently functional mRNA-engineered HBV-TCR T cells.</p><p><strong>Results: </strong>We demonstrated that a simple pulsing of whole blood with a peptide corresponding to the epitope recognized by the specific HBV-TCR elicited Th1 cytokine secretion in both patients only after HBV-TCR T cell treatment and not before. The amount of cytokines secreted also showed an infusion-dose-dependent association.</p><p><strong>Discussions: </strong>These findings support the utility of the whole blood cytokine release assay in monitoring the <i>in vivo</i> function and quantity of engineered T cell products following adoptive transfer.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"4 1","pages":"ltae007"},"PeriodicalIF":4.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advancements in nuclear imaging using radiolabeled nanobody tracers to support cancer immunotherapy. 利用放射性标记纳米抗体示踪剂支持癌症免疫疗法的核成像进展。
IF 4.1
Immunotherapy advances Pub Date : 2024-08-26 eCollection Date: 2024-01-01 DOI: 10.1093/immadv/ltae006
Katty Zeven, Yoline Lauwers, Lynn De Mey, Jens M Debacker, Tessa De Pauw, Timo W M De Groof, Nick Devoogdt
{"title":"Advancements in nuclear imaging using radiolabeled nanobody tracers to support cancer immunotherapy.","authors":"Katty Zeven, Yoline Lauwers, Lynn De Mey, Jens M Debacker, Tessa De Pauw, Timo W M De Groof, Nick Devoogdt","doi":"10.1093/immadv/ltae006","DOIUrl":"https://doi.org/10.1093/immadv/ltae006","url":null,"abstract":"<p><p>The evolving landscape of cancer immunotherapy has revolutionized cancer treatment. However, the dynamic tumor microenvironment has led to variable clinical outcomes, indicating a need for predictive biomarkers. Noninvasive nuclear imaging, using radiolabeled modalities, has aided in patient selection and monitoring of their treatment response. This approach holds promise for improving diagnostic accuracy, providing a more personalized treatment regimen, and enhancing the clinical response. Nanobodies or single-domain antibodies, derived from camelid heavy-chain antibodies, allow early timepoint detection of targets with high target-to-background ratios. To date, a plethora of nanobodies have been developed for nuclear imaging of tumor-specific antigens, immune checkpoints, and immune cells, both at a preclinical and clinical level. This review comprehensively outlines the recent advancements in nanobody-based nuclear imaging, both on preclinical and clinical levels. Additionally, the impact and expected future advancements on the use of nanobody-based radiopharmaceuticals in supporting cancer diagnosis and treatment follow-up are discussed.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"4 1","pages":"ltae006"},"PeriodicalIF":4.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regulation of temporal cytokine production by co-stimulation receptors in TCR-T cells is lost in CAR-T cells. 在 CAR-T 细胞中,TCR-T 细胞中的共刺激受体失去了对时间性细胞因子产生的调控。
IF 4.1
Immunotherapy advances Pub Date : 2024-06-19 eCollection Date: 2024-01-01 DOI: 10.1093/immadv/ltae004
Ashna Patel, Mikhail A Kutuzov, Michael L Dustin, P Anton van der Merwe, Omer Dushek
{"title":"Regulation of temporal cytokine production by co-stimulation receptors in TCR-T cells is lost in CAR-T cells.","authors":"Ashna Patel, Mikhail A Kutuzov, Michael L Dustin, P Anton van der Merwe, Omer Dushek","doi":"10.1093/immadv/ltae004","DOIUrl":"10.1093/immadv/ltae004","url":null,"abstract":"<p><p>CD8+ T cells contribute to immune responses by producing cytokines when their T-cell receptors (TCRs) recognise peptide antigens on major-histocompability-complex class I. However, excessive cytokine production can be harmful. For example, cytokine release syndrome is a common toxicity observed in treatments that activate T cells, including chimeric antigen receptor (CAR)-T-cell therapy. While the engagement of costimulatory receptors is well known to enhance cytokine production, we have limited knowledge of their ability to regulate the kinetics of cytokine production by CAR-T cells. Here we compare early (0-12 h) and late (12-20 h) production of IFN-gg, IL-2, and TNF-a production by T cells stimulated via TCR or CARs in the presence or absence ligands for CD2, LFA-1, CD28, CD27, and 4-1BB. For T cells expressing TCRs and 1st-generation CARs, activation by antigen alone was sufficient to stimulate early cytokine production, while co-stimulation by CD2 and 4-1BB was required to maintain late cytokine production. In contrast, T cells expressing 2nd-generation CARs, which have intrinsic costimulatory signalling motifs, produce high levels of cytokines in both early and late periods in the absence of costimulatory receptor ligands. Losing the requirement for costimulation for sustained cytokine production may contribute to the effectiveness and/or toxicity of 2nd-generation CAR-T-cell therapy.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"4 1","pages":"ltae004"},"PeriodicalIF":4.1,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cancer Vaccines: From an immunology perspective 癌症疫苗:从免疫学角度看
Immunotherapy advances Pub Date : 2023-12-21 DOI: 10.1093/immadv/ltad030
Shania Makker, Charlotte Galley, Clare L. Bennett
{"title":"Cancer Vaccines: From an immunology perspective","authors":"Shania Makker, Charlotte Galley, Clare L. Bennett","doi":"10.1093/immadv/ltad030","DOIUrl":"https://doi.org/10.1093/immadv/ltad030","url":null,"abstract":"\u0000 The concept of a therapeutic cancer vaccine to activate anti-tumour immunity pre-dates innovations in checkpoint blockade immunotherapies. However, vaccination strategies have yet to show the hoped-for successes in patients, and unanswered questions regarding the underlying immunological mechanisms behind cancer vaccines have hampered translation to clinical practice. Recent advances in our understanding of the potential of tumour mutational burden and neo-antigen-reactive T cells for response to immunotherapy have re-ignited enthusiasm for cancer vaccination strategies, coupled with the development of novel mRNA-based vaccines following successes in prevention of COVID-19. Here we summarise current developments in cancer vaccines and discuss how advances in our comprehension of the cellular interplay in immunotherapy-responsive tumours may inform better design of therapeutic cancer vaccines, with a focus on the role of dendritic cells (DCs) as the orchestrators of anti-tumour immunity. The increasing number of clinical trials and research being funnelled into cancer vaccines has demonstrated the ‘proof-of-principle’, supporting the hypothesis that therapeutic vaccines have potential as an immuno-oncology agent. For efficacious and safe cancer vaccines to be developed, better understanding of the underpinning immunological mechanisms is paramount.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"36 20","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138948858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ex Vivo Comparative Immunogenicity Assessment (EVCIA) to Determine Relative Immunogenicity in Chronic Plaque Psoriasis in Participants Receiving Humira® or Undergoing Repeated Switches Between Humira® and AVT02 体内外比较免疫原性评估 (EVCIA),以确定接受 Humira® 治疗或在 Humira® 和 AVT02 之间反复转换的慢性斑块型银屑病患者的相对免疫原性
Immunotherapy advances Pub Date : 2023-12-21 DOI: 10.1093/immadv/ltad029
Kathleen Richter, H. Haliduola, Jana Schockaert, Aurélie Mazy, N. Reznichenko, Eric Guenzi, Fausto Berti
{"title":"Ex Vivo Comparative Immunogenicity Assessment (EVCIA) to Determine Relative Immunogenicity in Chronic Plaque Psoriasis in Participants Receiving Humira® or Undergoing Repeated Switches Between Humira® and AVT02","authors":"Kathleen Richter, H. Haliduola, Jana Schockaert, Aurélie Mazy, N. Reznichenko, Eric Guenzi, Fausto Berti","doi":"10.1093/immadv/ltad029","DOIUrl":"https://doi.org/10.1093/immadv/ltad029","url":null,"abstract":"\u0000 Immunogenicity against biologic medicines is ubiquitous, and it is traditionally measured by the final humoral response. However, the onset of a sustained immunogenic response begins at the cellular level with activation of T cells and maturation of naïve B cells into plasma cells. Ex vivo comparative immunogenicity assessment (EVCIA) of cellular immunogenicity in participants with moderate-to-severe chronic plaque psoriasis in the AVT02-GL-302 study, who received either reference product (RP) alone (non-switching arm) or switched between RP and AVT02 (switching arm) after 1: 1 randomization at week 12. Peripheral blood mononuclear cells (PBMCs) were collected and cryopreserved from 28 participants at: baseline (before treatment) (week 1); pre-randomization (week 12); and week 16 and week 28 in both switching and non-switching arms. PBMCs were thawed and re-exposed to either medium alone (negative control), RP, AVT02, keyhole limpet hemocyanin (KLH) (positive control), RP+KLH, or AVT02+KLH. Samples from 10 participants (predetermined average cell viability of 75% across all timepoints) from each arm were analyzed for cytokine release after 24 hours and for Th-cell proliferation, 6 days post-seeding. Until week 28, cytokine release and Th-cell proliferation was similar at all time points in both switching and non-switching arms. Overall cellular immune response was elevated post-KLH re-exposure at all timepoints. The comparable ex vivo cellular immunogenicity between switching and non-switching arms complements the confirmation of interchangeability in the main study. Given the sensitivity of novel EVCIA, detecting cellular immunogenicity could be a potential outcome in predicting the immunogenicity of biologic medicines.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"49 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138949370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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