Immunotherapy advances最新文献

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 in vivo 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":"Introduction: The clinical efficacy of chimeric antigen and T cell receptor (TCR) T cell immunotherapies is attributed to their ability to proliferate and persist in vivo. 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.Materials and methods: We sought to achieve this by adapting a recently developed Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapid whole blood T cell assay to stimulate engineered TCR T cells in small volumes of whole blood (<1 ml) without in vitro 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.Results: 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.Discussions: These findings support the utility of the whole blood cytokine release assay in monitoring the in vivo function and quantity of engineered T cell products following adoptive transfer.","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":"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.","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":"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.","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

Harnessing natural killer cell effector function against cancer 利用自然杀伤细胞效应功能对抗癌症

Immunotherapy advances Pub Date : 2023-12-21 DOI: 10.1093/immadv/ltad031

Matthew D. Blunt, S. Khakoo

引用次数: 0

Strategies to overcome low MHC-I expression in paediatric and adult tumours. 克服儿童和成人肿瘤中 MHC-I 低表达的策略。

Immunotherapy advances Pub Date : 2023-12-11 eCollection Date: 2024-01-01 DOI: 10.1093/immadv/ltad028

J Guillaume, A Perzolli, M Boes

{"title":"Strategies to overcome low MHC-I expression in paediatric and adult tumours.","authors":"J Guillaume, A Perzolli, M Boes","doi":"10.1093/immadv/ltad028","DOIUrl":"10.1093/immadv/ltad028","url":null,"abstract":"Immunotherapy has made significant advancements in cancer treatments, improving patients' survival rates and quality of life. Several challenges still need to be addressed, which include the considerable fraction of incomplete curative responses in cancer patients, the development of therapy resistance by tumours, and the occurrence of adverse effects, such as inflammatory and autoimmune complications. Paediatric tumours usually exhibit lower responsiveness to immunotherapies compared to adult tumours. Although the underlying reasons are not yet fully understood, one known mechanism by which tumours avoid immune recognition is through reduced cell surface expression of major histocompatibility complex class I (MHC-I) complexes. Accordingly, the reduced presentation of neoantigens by MHC-I hinders the recognition and targeting of tumour cells by CD8+ T cells, impeding T-cell-mediated cytotoxic anti-tumour responses. MHC-I downregulation indeed often correlates with a poorer prognosis and diminished response to immunotherapy. Understanding the mechanisms underlying MHC-I downregulation in different types of paediatric and adult tumours is crucial for developing strategies to restore MHC-I expression and enhance anti-tumour immune responses. We here discuss progress in MHC-I-based immunotherapies against cancers.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"4 1","pages":"ltad028"},"PeriodicalIF":0.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466971","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

Janus kinase inhibitors ameliorate clinical symptoms in patients with STAT3 gain-of-function Janus激酶抑制剂可改善STAT3功能增益患者的临床症状

Immunotherapy advances Pub Date : 2023-11-24 DOI: 10.1093/immadv/ltad027

Shuya Kaneko, Fumiaki Sakura, Kay Tanita, A. Shimbo, R. Nambu, Masashi Yoshida, Shuichiro Umetsu, A. Inui, Chizuru Okada, M. Tsumura, Mamiko Yamada, Hisato Suzuki, K. Kosaki, Osamu Ohara, M. Shimizu, Tomohiro Morio, Satoshi Okada, H. Kanegane

{"title":"Janus kinase inhibitors ameliorate clinical symptoms in patients with STAT3 gain-of-function","authors":"Shuya Kaneko, Fumiaki Sakura, Kay Tanita, A. Shimbo, R. Nambu, Masashi Yoshida, Shuichiro Umetsu, A. Inui, Chizuru Okada, M. Tsumura, Mamiko Yamada, Hisato Suzuki, K. Kosaki, Osamu Ohara, M. Shimizu, Tomohiro Morio, Satoshi Okada, H. Kanegane","doi":"10.1093/immadv/ltad027","DOIUrl":"https://doi.org/10.1093/immadv/ltad027","url":null,"abstract":"Germline gain-of-function (GOF) variants in the signal transducer and activator of transcription 3 (STAT3) gene is an inborn error of immunity presenting with autoimmunity and lymphoproliferation. Symptoms can vary widely, and no effective treatment has been established. This study investigated the efficacy of Janus kinase (JAK) inhibitors (JAKi) in patients with STAT3-GOF. Four patients were enrolled and their clinical symptoms before and after the initiation of treatment with JAKi were described. A cell stimulation assay was performed using Epstein-Barr virus transformed lymphoid cell lines (EBV-LCLs) that were derived from the patients with STAT3-GOF. The patients presented with various symptoms, and these symptoms were mostly improved after the initiation of JAKi treatment. Upon interleukin-6 stimulation, the EBV-LCLs of patients showed enhanced STAT3 phosphorylation compare with those of the EBV-LCLs of healthy controls. In conclusion, four Japanese patients with STAT3-GOF were successfully treated with JAKi. JAKi ameliorated various symptoms and therefore, the use of JAKi could be an effective treatment option for patients with STAT3-GOF.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"18 2-3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139240349","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

Efficacy of PD-1 checkpoint inhibitor therapy in melanoma and beyond: are peripheral T cell phenotypes the key? PD-1检查点抑制剂治疗黑色素瘤及其他疾病的疗效:外周T细胞表型是关键吗?

Immunotherapy advances Pub Date : 2023-11-22 eCollection Date: 2023-01-01 DOI: 10.1093/immadv/ltad026

Katie R Flaherty, Stephanie Kucykowicz, Johannes Schroth, Will Traves, Kyle T Mincham, George E Finney

引用次数: 0

DC-targeting Lentivectors for Cancer Immunotherapy 肿瘤免疫治疗的dc靶向慢载体

Immunotherapy advances Pub Date : 2023-11-01 DOI: 10.1093/immadv/ltad023

Ester Gea-Mallorquí, Sarah Rowland-Jones

{"title":"DC-targeting Lentivectors for Cancer Immunotherapy","authors":"Ester Gea-Mallorquí, Sarah Rowland-Jones","doi":"10.1093/immadv/ltad023","DOIUrl":"https://doi.org/10.1093/immadv/ltad023","url":null,"abstract":"Abstract Lentivectors (LVs) induce sustained transgene expression and are attractive vaccine platforms for complex immune scenarios like cancer and persistent infections. This review summarises the literature on lentivectors with potential uses for in vivo immunotherapy, focusing on those targeting the most potent antigen-presenting cells: dendritic cells (DCs). There is a growing interest in myeloid-targeting therapies as, by influencing an early stage in the immune hierarchy, they can orchestrate a more diverse and complex targeted immune response. We dissect the nature of DC-targeting LVs and their induced immune responses to understand the state of the art, identify the knowledge gaps and guide efforts to maximise the generation of potent and effective immune responses. Lentivector-based vaccines provide several advantages over other vaccine platforms, such as directed tropism and limited vector immunogenicity, and have been shown to generate effective and sustained immune responses. Overall, DC-targeting lentivectors stand out as promising tools to be exploited in cancer immunotherapy, and new-generation LVs can further exploit the gained knowledge in the study of naturally-occurring lentiviruses for a more directed and adjuvanted response.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"4 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135510226","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