Immunotherapy advances最新文献_第4页

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":null,"pages":null},"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

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":null,"pages":null},"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

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

引用次数: 0

Leveraging the lymphohematopoietic graft-versus-host reaction (LGVHR) to achieve allograft tolerance and restore self tolerance with minimal toxicity. 利用淋巴造血移植物抗宿主反应(LGVHR)实现同种异体移植物耐受并以最小的毒性恢复自身耐受。

Immunotherapy advances Pub Date : 2023-01-01 DOI: 10.1093/immadv/ltad008

Megan Sykes

引用次数: 0

Human Infection Challenge in the Pandemic Era and Beyond, HIC-Vac annual meeting report, 2022 大流行时代及以后的人类感染挑战，HIC-Vac年度会议报告，2022年

Immunotherapy advances Pub Date : 2023-01-01 DOI: 10.1093/immadv/ltad024

Megan V C Barnes, Anika Mandla, Emma Smith, Maija Maskuniitty, Peter J M Openshaw

{"title":"Human Infection Challenge in the Pandemic Era and Beyond, HIC-Vac annual meeting report, 2022","authors":"Megan V C Barnes, Anika Mandla, Emma Smith, Maija Maskuniitty, Peter J M Openshaw","doi":"10.1093/immadv/ltad024","DOIUrl":"https://doi.org/10.1093/immadv/ltad024","url":null,"abstract":"Summary HIC-Vac is an international network of researchers dedicated to developing human infection challenge studies to accelerate vaccine development against pathogens of high global impact. The HIC-Vac Annual Meeting (3rd and 4th November 2022) brought together stakeholders including researchers, ethicists, volunteers, policymakers, industry partners, and funders with a strong representation from low- and middle-income countries. The network enables sharing of research findings, especially in endemic regions. Discussions included pandemic preparedness and the role of human challenge to accelerate vaccine development during outbreak, with industry speakers emphasising the great utility of human challenge in vaccine development. Public consent, engagement, and participation in human challenge studies were addressed, along with the role of embedded social science and empirical studies to uncover social, ethical, and regulatory issues around human infection challenge studies. Study volunteers shared their experiences and motivations for participating in studies. This report summarises completed and ongoing human challenge studies across a variety of pathogens and demographics, and addresses other key issues discussed at the meeting.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135447286","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

Combination therapies for the optimisation of Bispecific T-cell Engagers in cancer treatment. 优化双特异性t细胞接合体在癌症治疗中的联合疗法。

Immunotherapy advances Pub Date : 2023-01-01 DOI: 10.1093/immadv/ltad013

Winston M Zhu, Mark R Middleton

引用次数: 1

Correction to: Peripheral blood persistence and expansion of transferred non-genetically modified Natural Killer cells might not be necessary for clinical activity. 纠正:转移的非转基因自然杀伤细胞的外周血持久性和扩增可能对临床活动不是必需的。

Immunotherapy advances Pub Date : 2023-01-01 DOI: 10.1093/immadv/ltad003

引用次数: 0

Challenges in tolerogenic dendritic cell therapy for autoimmune diseases: the route of administration. 耐受性树突状细胞治疗自身免疫性疾病的挑战:给药途径。

Immunotherapy advances Pub Date : 2023-01-01 DOI: 10.1093/immadv/ltad012

María José Mansilla, Catharien M U Hilkens, Eva M Martínez-Cáceres

{"title":"Challenges in tolerogenic dendritic cell therapy for autoimmune diseases: the route of administration.","authors":"María José Mansilla, Catharien M U Hilkens, Eva M Martínez-Cáceres","doi":"10.1093/immadv/ltad012","DOIUrl":"https://doi.org/10.1093/immadv/ltad012","url":null,"abstract":"Tolerogenic dendritic cells (tolDCs) are a promising strategy to treat autoimmune diseases since they have the potential to re-educate and modulate pathological immune responses in an antigen-specific manner and, therefore, have minimal adverse effects on the immune system compared to conventional immunosuppressive treatments. TolDC therapy has demonstrated safety and efficacy in different experimental models of autoimmune disease, such as multiple sclerosis (MS), type 1 diabetes (T1D), and rheumatoid arthritis (RA). Moreover, data from phase I clinical trials have shown that therapy with tolDCs is safe and well tolerated by MS, T1D, and RA patients. Nevertheless, various parameters need to be optimized to increase tolDC efficacy. In this regard, one important parameter to be determined is the most appropriate route of administration. Several delivery routes, such as intravenous, subcutaneous, intraperitoneal, intradermal, intranodal, and intraarticular routes, have been used in experimental models as well as in phase I clinical trials. This review summarizes data obtained from preclinical and clinical studies of tolDC therapy in the treatment of MS, T1D, and RA and their animal models, as well as data from the context of cancer immunotherapy using mature peptide-loaded DC, and data from in vivo cell tracking experiments, to define the most appropriate route of tolDC administration in relation to the most feasible, safest, and effective therapeutic use.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10006351","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: 1

Impact of Fc receptors and host characteristics on myeloid phagocytic response to rituximab-treated 3D-cultured B-cell lymphoma Fc受体和宿主特性对利妥昔单抗治疗3d培养b细胞淋巴瘤骨髓吞噬反应的影响

Immunotherapy advances Pub Date : 2023-01-01 DOI: 10.1093/immadv/ltad025

Sandra Kleinau

{"title":"Impact of Fc receptors and host characteristics on myeloid phagocytic response to rituximab-treated 3D-cultured B-cell lymphoma","authors":"Sandra Kleinau","doi":"10.1093/immadv/ltad025","DOIUrl":"https://doi.org/10.1093/immadv/ltad025","url":null,"abstract":"Summary Antibody-based immunotherapy is successful in treating cancer, but its effectiveness varies among patients. Therefore, understanding myeloid phagocytic responses to therapeutic antibodies is critical. Immunoglobulin Fc receptors and host characteristics were evaluated in phagocytosis of 3D-cultured CD20+ B-cell lymphoma (spheroids) treated with different anti-CD20 rituximab (RTX) monoclonal antibody isotypes. Monocytes from healthy donors of different ages and sexes were isolated, and their Fc receptors for IgG (FcγRI, FcγRIIa, FcγRIIIa) and IgA (FcαRI) were determined, as well as Fc receptor gene polymorphisms. Antibody-dependent phagocytosis was assessed using flow cytometry, confocal imaging, and Fc receptor blocking. RTX isotypes showed varying efficacy in stimulating the phagocytosis of spheroids. RTX-IgG3 proved to be the most efficient, followed by RTX-IgG1. Monocytes infiltrated RTX-treated spheroids at the periphery but migrated also into the core when stimulated with RTX-IgG3. Blocking FcγRI or FcγRIIa, but not FcγRIIIa, with antibodies inhibited RTX-IgG1 and RTX-IgG3-mediated phagocytosis. Monocytes from younger women demonstrated higher FcγRI and FcγRIIa levels compared to older women, while older men displayed increasing FcγRI and FcγRIIIa levels compared to younger men. Monocytes from younger women displayed greater phagocytic activity compared to older women, while older men had better IgG-mediated phagocytosis than younger men. Single Fc receptor levels, or FcγRIIa and FcγRIIIa genetic variants, had a low correlation with phagocytic intensity, likely as a result of multiple engagements of Fcreceptors for IgG-mediated phagocytosis. In conclusion, antibody isotype, Fc receptors, age, and sex influence tumor phagocytosis. This study exposes the relationship between host traits and the efficacy of therapeutic antibodies, providing insights into cancer immunotherapy treatment.","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135447896","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

Immunology of allergen immunotherapy. 过敏原免疫疗法的免疫学。

IF 4.1

Immunotherapy advances Pub Date : 2022-11-25 eCollection Date: 2022-01-01 DOI: 10.1093/immadv/ltac022

Rifat S Rahman, Duane R Wesemann

引用次数: 0