Immunotherapy advances最新文献

{"title":"Correction to: Immunology of allergen immunotherapy.","authors":"","doi":"10.1093/immadv/ltad017","DOIUrl":"10.1093/immadv/ltad017","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/immadv/ltac022.].</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad017"},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10569372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41241803","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}

{"title":"Efficacy of smallpox vaccines against Mpox infections in humans.","authors":"Melissa M Christodoulidou, Neil A Mabbott","doi":"10.1093/immadv/ltad020","DOIUrl":"10.1093/immadv/ltad020","url":null,"abstract":"<p><p>The Mpox virus (MPXV) is endemic in certain countries in Central and West Africa, where several mammalian species, especially rodents, are natural reservoirs. However, the MPXV can infect nonhuman primates and cause zoonotic infections in humans after close contact with an infected animal. Human-to-human transmission of MPXV can also occur through direct close contact with an infected individual or infected materials. In May 2022 an initial cluster of human Mpox cases was identified in the UK, with the first case confirmed in a patient who had recently travelled to Nigeria. The infection subsequently spread via human-to-human transmission within the UK and Mpox cases began to appear in many other countries around the world where the MPXV is not endemic. No specific treatments for MPXV infection in humans are available. However, data from studies undertaken in Zaire in the 1980s revealed that those with a history of smallpox vaccination during the global smallpox eradication campaign also had good cross-protection against MPXV infection. However, the vaccines used during the global eradication campaign are no longer available. During the 2022 global Mpox outbreak over a million doses of the Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) smallpox vaccine were offered either as pre or postexposure prophylaxis to those at high risk of MPXV infection. Here, we review what has been learned about the efficacy of smallpox vaccines in reducing the incidence of MPXV infections in high-risk close contacts.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad020"},"PeriodicalIF":0.0,"publicationDate":"2023-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10598838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232684","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}

{"title":"Prevention vs treatment of rheumatoid arthritis.","authors":"Lars Klareskog, Lars Alfredsson","doi":"10.1093/immadv/ltad016","DOIUrl":"10.1093/immadv/ltad016","url":null,"abstract":"<p><p>Whether a yet chronic and not curable disease like rheumatoid arthritis (RA) can be subject to prevention or whether available resources should be focused on treatment is a classical dilemma. Similar to the case in most other chronic diseases, the focus in research as well as in clinical practice has been on the treatment of established diseases, resulting in drugs that are efficient in eliminating most joint damage but not able to cure the disease or stop needs for continuous treatment of the disease. Less effort has been spent on identifying and implementing ways to prevent the disease. We argue in this review that knowledge concerning the longitudinal evolvement of the major, 'seropositive' subset of RA has now come to a stage where prevention should be a large part of the research agenda and that we should prepare for prevention as part of clinical practice in RA. We describe briefly the knowledge basis for broad public health-based prevention as well as for a 'precision prevention' strategy. In the latter, individuals at high risk for RA will be identified, monitored, and ultimately provided with advice on how to change lifestyle/environment or be given treatment with drugs able to delay and ultimately stop the development of RA. Whether this potential of precision prevention for RA will change the broader clinical practice will depend on whether specific and long-lasting interference with disease-inducing immunity, ultimately 'tolerance therapy', will become a reality.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad016"},"PeriodicalIF":4.1,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10473452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10152728","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}

{"title":"Establishing a single-sex controlled human <i>Schistosoma mansoni</i> infection model for Uganda: protocol for safety and dose-finding trial.","authors":"Andrew Abaasa, Moses Egesa, Emmanuella Driciru, Jan Pieter R Koopman, Ronald Kiyemba, Richard E Sanya, Jacent Nassuuna, Agnes Ssali, Geofrey Kimbugwe, Anne Wajja, Govert J van Dam, Paul L A M Corstjens, Stephen Cose, Janet Seeley, Dorcas Kamuya, Emily L Webb, Maria Yazdanbakhsh, Pontiano Kaleebu, Afzal A Siddiqui, Narcis Kabatereine, Edridah Tukahebwa, Meta Roestenberg, Alison M Elliott","doi":"10.1093/immadv/ltad010","DOIUrl":"10.1093/immadv/ltad010","url":null,"abstract":"<p><p>Control of schistosomiasis depends on a single drug, praziquantel, with variable cure rates, high reinfection rates, and risk of drug resistance. A vaccine could transform schistosomiasis control. Preclinical data show that vaccine development is possible, but conventional vaccine efficacy trials require high incidence, long-term follow-up, and large sample size. Controlled human infection studies (CHI) can provide early efficacy data, allowing the selection of optimal candidates for further trials. A <i>Schistosoma</i> CHI has been established in the Netherlands but responses to infection and vaccines differ in target populations in endemic countries. We aim to develop a CHI for <i>Schistosoma mansoni</i> in Uganda to test candidate vaccines in an endemic setting. This is an open-label, dose-escalation trial in two populations: minimal, or intense, prior <i>Schistosoma</i> exposure. In each population, participants will be enrolled in sequential dose-escalating groups. Initially, three volunteers will be exposed to 10 cercariae. If all show infection, seven more will be exposed to the same dose. If not, three volunteers in subsequent groups will be exposed to higher doses (20 or 30 cercariae) following the same algorithm, until all 10 volunteers receiving a particular dose become infected, at which point the study will be stopped for that population. Volunteers will be followed weekly after infection until CAA positivity or to 12 weeks. Once positive, they will be treated with praziquantel and followed for one year. The trial registry number is ISRCTN14033813 and all approvals have been obtained. The trial will be subjected to monitoring, inspection, and/or audits.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad010"},"PeriodicalIF":4.1,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10396375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10314636","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}

{"title":"Blockade of innate inflammatory cytokines TNF<b>α</b>, IL-1<b>β</b>, or IL-6 overcomes virotherapy-induced cancer equilibrium to promote tumor regression.","authors":"Michael J Walsh, Lestat R Ali, Patrick Lenehan, Courtney T Kureshi, Rakeeb Kureshi, Michael Dougan, David M Knipe, Stephanie K Dougan","doi":"10.1093/immadv/ltad011","DOIUrl":"10.1093/immadv/ltad011","url":null,"abstract":"<p><p>Cancer therapeutics can lead to immune equilibrium in which the immune response controls tumor cell expansion without fully eliminating the cancer. The factors involved in this equilibrium remain incompletely understood, especially those that would antagonize the anti-tumor immune response and lead to tumor outgrowth. We previously demonstrated that continuous treatment with a non-replicating herpes simplex virus 1 expressing interleukin (IL)-12 induces a state of cancer immune equilibrium highly dependent on interferon-γ. We profiled the IL-12 virotherapy-induced immune equilibrium in murine melanoma, identifying blockade of innate inflammatory cytokines, tumor necrosis factor alpha (TNFα), IL-1β, or IL-6 as possible synergistic interventions. Antibody depletions of each of these cytokines enhanced survival in mice treated with IL-12 virotherapy and helped to overcome equilibrium in some tumors. Single-cell RNA-sequencing demonstrated that blockade of inflammatory cytokines resulted in downregulation of overlapping inflammatory pathways in macrophages, shifting immune equilibrium towards tumor clearance, and raising the possibility that TNFα blockade could synergize with existing cancer immunotherapies.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad011"},"PeriodicalIF":0.0,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9836301","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}

{"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":"10.1093/immadv/ltad006","url":null,"abstract":"<p><p>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 <i>in vitro</i> as well as <i>ex vivo</i>. 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.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad006"},"PeriodicalIF":4.1,"publicationDate":"2023-03-30","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}

{"title":"A systems approach evaluating the impact of SARS-CoV-2 variant of concern mutations on CD8+ T cell responses.","authors":"Paul R Buckley, Chloe H Lee, Agne Antanaviciute, Alison Simmons, Hashem Koohy","doi":"10.1093/immadv/ltad005","DOIUrl":"10.1093/immadv/ltad005","url":null,"abstract":"<p><p>T cell recognition of SARS-CoV-2 antigens after vaccination and/or natural infection has played a central role in resolving SARS-CoV-2 infections and generating adaptive immune memory. However, the clinical impact of SARS-CoV-2-specific T cell responses is variable and the mechanisms underlying T cell interaction with target antigens are not fully understood. This is especially true given the virus' rapid evolution, which leads to new variants with immune escape capacity. In this study, we used the Omicron variant as a model organism and took a systems approach to evaluate the impact of mutations on CD8+ T cell immunogenicity. We computed an immunogenicity potential score for each SARS-CoV-2 peptide antigen from the ancestral strain and Omicron, capturing both antigen presentation and T cell recognition probabilities. By comparing ancestral vs. Omicron immunogenicity scores, we reveal a divergent and heterogeneous landscape of impact for CD8+ T cell recognition of mutated targets in Omicron variants. While T cell recognition of Omicron peptides is broadly preserved, we observed mutated peptides with deteriorated immunogenicity that may assist breakthrough infection in some individuals. We then combined our scoring scheme with an <i>in silico</i> mutagenesis, to characterise the position- and residue-specific theoretical mutational impact on immunogenicity. While we predict many escape trajectories from the theoretical landscape of substitutions, our study suggests that Omicron mutations in T cell epitopes did not develop under cell-mediated pressure. Our study provides a generalisable platform for fostering a deeper understanding of existing and novel variant impact on antigen-specific vaccine- and/or infection-induced T cell immunity.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad005"},"PeriodicalIF":4.1,"publicationDate":"2023-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10112682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9386244","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}

{"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":"<p><p>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.</p>","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}

{"title":"Peripheral blood persistence and expansion of transferred non-genetically modified Natural Killer cells might not be necessary for clinical activity.","authors":"Lucia Silla","doi":"10.1093/immadv/ltac024","DOIUrl":"https://doi.org/10.1093/immadv/ltac024","url":null,"abstract":"<p><p>Natural killer (NK) cells are innate lymphocytes that react without previous exposition to virus infected or malignant cells and stimulate adaptive immune response to build a long-lasting immunity against it. To that end, tissue resident NK cells are predominantly regulatory as opposed to cytotoxic. In the hematopoietic stem cell transplant (HSCT) setting, which curative potential relies on the graft versus leukemia effect, NK cells are known to play a significant role. This knowledge has paved the way to the active investigation on its anti-tumor effect outside the stem cell transplant scenario. Based on the relevant literature on the adoptive transfer of non-genetically modified NK cells for the treatment of relapsed/refractory acute leukemia and on our own experience, we discuss the role of donor cell peripheral blood persistence and expansion and its lack of correlation with anti-leukemia activity.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltac024"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9885937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9320580","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}

{"title":"Lytic efficiency of immunosuppressive drug-resistant armoured T cells against circulating HBV-related HCC in whole blood.","authors":"Meiyin Lin,&nbsp;Sebastian Chakrit Bhakdi,&nbsp;Damien Tan,&nbsp;Joycelyn Jie Xin Lee,&nbsp;David Wai Meng Tai,&nbsp;Andrea Pavesi,&nbsp;Lu-En Wai,&nbsp;Tina Wang,&nbsp;Antonio Bertoletti,&nbsp;Anthony Tanoto Tan","doi":"10.1093/immadv/ltad015","DOIUrl":"https://doi.org/10.1093/immadv/ltad015","url":null,"abstract":"<p><p>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 <i>in vivo</i> 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.</p>","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}