{"title":"Correction to: Advancement of antigen-specific immunotherapy: knowledge transfer between allergy and autoimmunity.","authors":"","doi":"10.1093/immadv/ltad004","DOIUrl":"https://doi.org/10.1093/immadv/ltad004","url":null,"abstract":"[This corrects the article DOI: 10.1093/immadv/ltab009.].","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad004"},"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/40/15/ltad004.PMC10374272.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10255637","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 historical perspective on HLA.","authors":"Walter Bodmer","doi":"10.1093/immadv/ltad014","DOIUrl":"https://doi.org/10.1093/immadv/ltad014","url":null,"abstract":"<p><p>The discovery of the history of the HLA system is reviewed from the earliest attempts at cancer transfers between mice, through the discovery of the mouse H-2 system on mouse red blood cells, the discovery of HLA class II and II antigens by use of sera from multiparous women, to the resolution of the HLA and H-2 functions explained by the attachment of intra cellular peptides to the HLA antigen grooves on the cell surface. The study of the associations between HLA types and diseases forms the basis for the subsequent extensive study of the genetics of human complex disease and phenotypes by GWAS (Genome Wide Association Studies).</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad014"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10111124","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}
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<sup>+</sup> 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":"<p><strong>Introduction: </strong>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.</p><p><strong>Materials and methods: </strong>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 <i>in vitro</i> 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.</p><p><strong>Results: </strong>As such, we demonstrated recombinant proDer p 1 fusion proteins were selectively bound by Der p 1 reactive hybridomas as well as primary IgG1<sup>+</sup> 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 IC<sub>50</sub> values in the single digit nanomolar value, compared to the ADC.</p><p><strong>Discussions: </strong>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.</p>","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}
{"title":"Leveraging the lymphohematopoietic graft-versus-host reaction (LGVHR) to achieve allograft tolerance and restore self tolerance with minimal toxicity.","authors":"Megan Sykes","doi":"10.1093/immadv/ltad008","DOIUrl":"https://doi.org/10.1093/immadv/ltad008","url":null,"abstract":"<p><p>Mixed allogeneic chimerism has considerable potential to advance the achievement of immune tolerance to alloantigens for transplantation and the restoration of self-tolerance in patients with autoimmune disease. In this article, I review evidence that graft-versus-host (GVH) alloreactivity without graft-vs-host disease (GVHD), termed a lymphohematopoietic graft-vs-host reaction (LGVHR), can promote the induction of mixed chimerism with minimal toxicity. LGVHR was originally shown to occur in an animal model when non-tolerant donor lymphocytes were administered to mixed chimeras in the absence of inflammatory stimuli and was found to mediate powerful graft-vs-leukemia/lymphoma effects without GVHD. Recent large animal studies suggest a role for LGVHR in promoting durable mixed chimerism and the demonstration that LGVHR promotes chimerism in human intestinal allograft recipients has led to a pilot study aiming to achieve durable mixed chimerism.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad008"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9866301","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}
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":"28 1","pages":"0"},"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}
{"title":"Combination therapies for the optimisation of Bispecific T-cell Engagers in cancer treatment.","authors":"Winston M Zhu, Mark R Middleton","doi":"10.1093/immadv/ltad013","DOIUrl":"https://doi.org/10.1093/immadv/ltad013","url":null,"abstract":"<p><p>Bispecific T-cell engagers (BiTEs) redirect endogenous T-cell populations to cells expressing tumour-associated antigens to induce tumour cell killing. This inherently relies upon a cytotoxic T-cell population that is able to be recruited. In many cancers, immune checkpoints and other immunosuppressive factors in the tumour microenvironment lead to a population of anergic T-cells which cannot be redirected to tumour killing and thus impede the efficacy of BiTE therapy. Furthermore, there is evidence that BiTE therapy itself can increase immune checkpoint expression, and this is thought to be a major escape mechanism for the BiTE therapy blinatumomab. To overcome these inadequate T-cell responses, BiTEs may be combined with checkpoint inhibitors, chemotherapy, costimulatory molecules or oncolytic viruses. Study of these combinations is needed to expand the use of BiTEs in solid malignancies. This review covers the rationale, preclinical evidence and any clinical trials for these combination therapies and a few other less-studied combinations.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad013"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10045659","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}
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":"<p><p>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 <i>in vivo</i> cell tracking experiments, to define the most appropriate route of tolDC administration in relation to the most feasible, safest, and effective therapeutic use.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad012"},"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}
{"title":"Correction to: Peripheral blood persistence and expansion of transferred non-genetically modified Natural Killer cells might not be necessary for clinical activity.","authors":"","doi":"10.1093/immadv/ltad003","DOIUrl":"https://doi.org/10.1093/immadv/ltad003","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/immadv/ltac024.].</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"3 1","pages":"ltad003"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9938634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9317021","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":"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":"1 1","pages":"0"},"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}
Immunotherapy advancesPub Date : 2022-11-25eCollection Date: 2022-01-01DOI: 10.1093/immadv/ltac022
Rifat S Rahman, Duane R Wesemann
{"title":"Immunology of allergen immunotherapy.","authors":"Rifat S Rahman, Duane R Wesemann","doi":"10.1093/immadv/ltac022","DOIUrl":"10.1093/immadv/ltac022","url":null,"abstract":"<p><p>Allergen immunotherapy (AIT) is the only disease-modifying therapy for allergic disease. Through repeated inoculations of low doses of allergen-either as whole proteins or peptides-patients can achieve a homeostatic balance between inflammatory effectors induced and/or associated with allergen contact, and mediators of immunologic non-responsiveness, potentially leading to sustained clinical improvements. AIT for airborne/respiratory tract allergens and insect venoms have traditionally been supplied subcutaneously, but other routes and modalities of administration can also be effective. Despite differences of allergen administration, there are some similarities of immunologic responses across platforms, with a general theme involving the restructuring and polarization of adaptive and innate immune effector cells. Here we review the immunology of AIT across various delivery platforms, including subcutaneous, sublingual, epicutaneous, intradermal, and intralymphatic approaches, emphasizing shared mechanisms associated with achieving immunologic non-responsiveness to allergen.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"2 1","pages":"ltac022"},"PeriodicalIF":4.1,"publicationDate":"2022-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9749131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10765400","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}