Immunotherapy advances最新文献_第3页

Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood. 利用外周血治疗前后的免疫分型对黑色素瘤的 PD-1 阻断反应进行分层。

Immunotherapy advances Pub Date : 2023-01-06 eCollection Date: 2023-01-01 DOI: 10.1093/immadv/ltad001

Natalie M Edner, Elisavet Ntavli, Lina Petersone, Chun Jing Wang, Astrid Fabri, Alexandros Kogimtzis, Vitalijs Ovcinnikovs, Ellen M Ross, Frank Heuts, Yassin Elfaki, Luke P Houghton, Toby Talbot, Amna Sheri, Alexandra Pender, David Chao, Lucy S K Walker

{"title":"Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood.","authors":"Natalie M Edner, Elisavet Ntavli, Lina Petersone, Chun Jing Wang, Astrid Fabri, Alexandros Kogimtzis, Vitalijs Ovcinnikovs, Ellen M Ross, Frank Heuts, Yassin Elfaki, Luke P Houghton, Toby Talbot, Amna Sheri, Alexandra Pender, David Chao, Lucy S K Walker","doi":"10.1093/immadv/ltad001","DOIUrl":"10.1093/immadv/ltad001","url":null,"abstract":"Efficacy of checkpoint inhibitor therapies in cancer varies greatly, with some patients showing complete responses while others do not respond and experience progressive disease. We aimed to identify correlates of response and progression following PD-1-directed therapy by immunophenotyping peripheral blood samples from 20 patients with advanced malignant melanoma before and after treatment with the PD-1 blocking antibody pembrolizumab. Our data reveal that individuals responding to PD-1 blockade were characterised by increased CD8 T cell proliferation following treatment, while progression was associated with an increase in CTLA-4-expressing Treg. Remarkably, unsupervised clustering analysis of pre-treatment T cell subsets revealed differences in individuals that went on to respond to PD-1 blockade compared to individuals that did not. These differences mapped to expression of the proliferation marker Ki67 and the costimulatory receptor CD28 as well as the inhibitory molecules 2B4 and KLRG1. While these results require validation in larger patient cohorts, they suggest that flow cytometric analysis of a relatively small number of T cell markers in peripheral blood could potentially allow stratification of PD-1 blockade treatment response prior to therapy initiation.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad001"},"PeriodicalIF":0.0,"publicationDate":"2023-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9929715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10773190","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

Peripheral blood persistence and expansion of transferred non-genetically modified Natural Killer cells might not be necessary for clinical activity. 转移的非转基因自然杀伤细胞的外周血持续和扩增可能不是临床活动所必需的。

Immunotherapy advances Pub Date : 2023-01-01 DOI: 10.1093/immadv/ltac024

Lucia Silla

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Lytic efficiency of immunosuppressive drug-resistant armoured T cells against circulating HBV-related HCC in whole blood. 免疫抑制耐药装甲T细胞对循环hbv相关HCC的全血溶解效率。

Immunotherapy advances Pub Date : 2023-01-01 DOI: 10.1093/immadv/ltad015

Meiyin Lin, Sebastian Chakrit Bhakdi, Damien Tan, Joycelyn Jie Xin Lee, David Wai Meng Tai, Andrea Pavesi, Lu-En Wai, Tina Wang, Antonio Bertoletti, Anthony Tanoto Tan

{"title":"Lytic efficiency of immunosuppressive drug-resistant armoured T cells against circulating HBV-related HCC in whole blood.","authors":"Meiyin Lin, Sebastian Chakrit Bhakdi, Damien Tan, Joycelyn Jie Xin Lee, David Wai Meng Tai, Andrea Pavesi, Lu-En Wai, Tina Wang, Antonio Bertoletti, Anthony Tanoto Tan","doi":"10.1093/immadv/ltad015","DOIUrl":"https://doi.org/10.1093/immadv/ltad015","url":null,"abstract":"Recurrence of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) after liver transplant (LT) is mediated by circulating tumour cells (CTCs) and exacerbated by the immunosuppressants required to prevent graft rejection. To circumvent the effects of immunosuppressants, we developed immunosuppressive drug-resistant armoured HBV-specific T-cell receptor-redirected T cells (IDRA HBV-TCR). However, their ability to eliminate HBV-HCC circulating in the whole blood has never been tested, and whether their lytic efficacy is compatible with the number of adoptively transferred T cells in vivo has never been measured. Hence, we developed a microscopy-based assay to quantify CTCs in whole blood. The assay was then used to quantify the efficacy of IDRA HBV-TCRs to lyse free-floating HBV-HCC cells in the presence of Tacrolimus and Mycophenolate Mofetil (MMF). We demonstrated that a panel of antibodies (AFP, GPC3, Vimentin, pan-Cytokeratin, and CD45) specific for HCC tumour antigens and immune cells can effectively differentiate HCC-CTCs in whole blood. Through dose-titration experiments, we observed that in the presence of immunosuppressive drugs, a minimum of 20 000 IDRA HBV-TCR T cells/ml of whole blood is necessary to lyse ~63.5% of free-floating HBV-HCC cells within 16 hours. In conclusion, IDRA HBV-TCR T cells can lyse free-floating HBV-HCC cells in whole blood in the presence of Tacrolimus and MMF. The quantity of IDRA-HBV TCR T cells required can be achieved by the adoptive transfer of 5 × 106 IDRA-HBV TCR-T cells/kg, supporting the utilisation of IDRA HBV-TCR T cells to eliminate CTCs as prophylaxis against recurrence after LT.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad015"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/19/10/ltad015.PMC10460197.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10109074","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

Treg-based immunotherapy for antigen-specific immune suppression and stable tolerance induction: a perspective. 基于treg的免疫疗法对抗原特异性免疫抑制和稳定耐受诱导的研究进展

Immunotherapy advances Pub Date : 2023-01-01 DOI: 10.1093/immadv/ltad007

Shimon Sakaguchi, Ryoji Kawakami, Norihisa Mikami

{"title":"Treg-based immunotherapy for antigen-specific immune suppression and stable tolerance induction: a perspective.","authors":"Shimon Sakaguchi, Ryoji Kawakami, Norihisa Mikami","doi":"10.1093/immadv/ltad007","DOIUrl":"https://doi.org/10.1093/immadv/ltad007","url":null,"abstract":"FoxP3-expressing regulatory T cells (Tregs), whether naturally generated in the immune system or unnaturally induced from conventional T cells (Tconvs) in the laboratory, have much therapeutic value in treating immunological diseases and establishing transplantation tolerance. Natural Tregs (nTregs) can be selectively expanded in vivo by administration of low-dose IL-2 or IL-2 muteins for immune suppression. For adoptive Treg cell therapy, nTregs can be expanded in vitro by strong antigenic stimulation in the presence of IL-2. Synthetic receptors such as CAR can be expressed in nTregs to equip them with a particular target specificity for suppression. In addition, antigen-specific Tconvs can be converted in vitro to functionally stable Treg-like cells by a combination of antigenic stimulation, FoxP3 induction, and establishment of the Treg-type epigenome. This review discusses current and prospective strategies for Treg-based immune suppression and the issues to be resolved for achieving stable antigen-specific immune suppression and tolerance induction in the clinic by targeting Tregs.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad007"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0d/65/ltad007.PMC10309084.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10123148","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

TIGIT-based immunotherapeutics in lung cancer. 基于tigit的肺癌免疫治疗。

Immunotherapy advances Pub Date : 2023-01-01 DOI: 10.1093/immadv/ltad009

Akshay J Patel, Gary W Middleton

引用次数: 0

Correction to: Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor. 更正:sabatolimab的特性，一种针对TIM-3受体具有免疫髓系活性的新型免疫疗法。

Immunotherapy advances Pub Date : 2023-01-01 DOI: 10.1093/immadv/ltad002

引用次数: 0

Combination CD200R/PD-1 blockade in a humanised mouse model. CD200R/PD-1在人源化小鼠模型中的联合阻断作用。

Immunotherapy advances Pub Date : 2023-01-01 DOI: 10.1093/immadv/ltad006

Martin Fellermeyer, Consuelo Anzilotti, Christopher Paluch, Richard J Cornall, Simon J Davis, Uzi Gileadi

{"title":"Combination CD200R/PD-1 blockade in a humanised mouse model.","authors":"Martin Fellermeyer, Consuelo Anzilotti, Christopher Paluch, Richard J Cornall, Simon J Davis, Uzi Gileadi","doi":"10.1093/immadv/ltad006","DOIUrl":"https://doi.org/10.1093/immadv/ltad006","url":null,"abstract":"There is an increasing number of immune-checkpoint inhibitors being developed and approved for cancer immunotherapy. Most of the new therapies aim to reactivate tumour-infiltrating T cells, which are responsible for tumour killing. However, in many tumours, the most abundant infiltrating immune cells are macrophages and myeloid cells, which can be tumour-promoting as well as tumouricidal. CD200R was initially identified as a myeloid-restricted, inhibitory immune receptor, but was subsequently also found to be expressed within the lymphoid lineage. Using a mouse model humanised for CD200R and PD-1, we investigated the potential of a combination therapy comprising nivolumab, a clinically approved PD-1 blocking antibody, and OX108, a CD200R antagonist. We produced nivolumab as a murine IgG1 antibody and validated its binding activity in vitro as well as ex vivo. We then tested the combination therapy in the immunogenic colorectal cancer model MC38 as well as the PD-1 blockade-resistant lung cancer model LLC1, which is characterised by a large number of infiltrating myeloid cells, making it an attractive target for CD200R blockade. No significant improvement of overall survival was found in either model, compared to nivolumab mIgG1 monotherapy. There was a trend for more complete responses in the MC38 model, but investigation of the infiltrating immune cells failed to account for this. Importantly, MC38 cells expressed low levels of CD200, whereas LLC1 cells were CD200-negative. Further investigation of CD200R-blocking antibodies in tumours expressing high levels of CD200 could be warranted.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad006"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10112683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9386243","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

Correction to: Advancement of antigen-specific immunotherapy: knowledge transfer between allergy and autoimmunity. 抗原特异性免疫治疗的进展:过敏和自身免疫之间的知识转移。

Immunotherapy advances Pub Date : 2023-01-01 DOI: 10.1093/immadv/ltad004

引用次数: 0

A historical perspective on HLA. HLA的历史观点。

Immunotherapy advances Pub Date : 2023-01-01 DOI: 10.1093/immadv/ltad014

Walter Bodmer

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A recombinant Der p 1-specific allergen-toxin demonstrates superior killing of allergen-reactive IgG⁺ hybridomas in comparison to its recombinant allergen-drug conjugate. 与重组的过敏原-药物偶联物相比，重组的Der 1特异性过敏原毒素对过敏原反应性IgG+杂交瘤的杀伤能力更强。

Immunotherapy advances Pub Date : 2023-01-01 DOI: 10.1093/immadv/ltac023

A K Daramola, O A Akinrinmade, E A Fajemisin, K Naran, N Mthembu, S Hadebe, F Brombacher, A M Huysamen, O E Fadeyi, R Hunter, S Barth

{"title":"A recombinant Der p 1-specific allergen-toxin demonstrates superior killing of allergen-reactive IgG+ hybridomas in comparison to its recombinant allergen-drug conjugate.","authors":"A K Daramola, O A Akinrinmade, E A Fajemisin, K Naran, N Mthembu, S Hadebe, F Brombacher, A M Huysamen, O E Fadeyi, R Hunter, S Barth","doi":"10.1093/immadv/ltac023","DOIUrl":"https://doi.org/10.1093/immadv/ltac023","url":null,"abstract":"Introduction: Current treatments for asthma help to alleviate clinical symptoms but do not cure the disease. In this study, we explored a novel therapeutic approach for the treatment of house dust mite allergen Der p 1induced asthma by aiming to eliminate specific population of B-cells involved in memory IgE response to Der p 1.Materials and methods: To achieve this aim, we developed and evaluated two different proDer p 1-based fusion proteins; an allergen-toxin (proDer p 1-ETA) and an allergen-drug conjugate (ADC) (proDer p 1-SNAP-AURIF) against Der p 1 reactive hybridomas as an in vitro model for Der p 1 reactive human B-cells. The strategy involved the use of proDer p 1 allergen as a cell-specific ligand to selectively deliver the bacterial protein toxin Pseudomonas exotoxin A (ETA) or the synthetic small molecule toxin Auristatin F (AURIF) into the cytosol of Der p 1 reactive cells for highly efficient cell killing.Results: As such, we demonstrated recombinant proDer p 1 fusion proteins were selectively bound by Der p 1 reactive hybridomas as well as primary IgG1+ B-cells from HDM-sensitized mice. The therapeutic potential of proDer p 1-ETA' and proDer p 1-SNAP-AURIF was confirmed by their selective cytotoxic activities on Der p 1 reactive hybridoma cells. The allergen-toxin demonstrated superior cytotoxic activity, with IC50 values in the single digit nanomolar value, compared to the ADC.Discussions: Altogether, the proof-of-concept experiments in this study provide a promising approach for the treatment of patients with house dust mite-driven allergic asthma.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltac023"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9912260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10738268","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