Immunotherapy advances最新文献

{"title":"CAR-T cell-induced cytokine release syndrome is rapidly alleviated by Tripterygium glycosides: a case series and laboratory examination study.","authors":"Zuqiong Xu, Fang Tian, Biqing Chen, Xiangtu Kong, Xingbin Dai, Jiang Cao, Pengjun Jiang, Xuejun Zhu","doi":"10.1093/immadv/ltag021","DOIUrl":"10.1093/immadv/ltag021","url":null,"abstract":"<p><strong>Background: </strong>Cytokine release syndrome (CRS) is a life-threatening complication of chimeric antigen receptor T cell (CAR-T) therapy. Macrophages/monocytes are mediators of CRS. Tripterygium glycosides is an immunomodulator, which could inhibit macrophages/monocytes in animal models.</p><p><strong>Methods: </strong>Two patients with relapsed and refractory hematological malignancies developed CRS after receiving CAR-T therapy. They received short-term Tripterygium glycosides orally.</p><p><strong>Results: </strong>Both patients showed rapid mitigation of fever with evidently decrease in elevated inflammatory cytokines within 72 hours. The patients' monocytes diminished remarkably, while CAR-T cells were negligibly affected. Treatment of 30 ng/ml triptolide in <i>ex vivo</i> cultured patients' blood for 24 hours selectively deplete over half of monocytes. Single-cell RNA sequencing suggested selective depletion of CD14 ⁺ CD16⁺ monocytes with decreased pro-inflammatory cytokines.</p><p><strong>Conclusion: </strong>The low-cost and orally available Tripterygium glycosides could be a promising alternative for CAR-T induced CRS, as well as other diseases complicated with CRS, e.g. coronavirus disease 2019.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"6 1","pages":"ltag021"},"PeriodicalIF":4.4,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217404","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":"L-Arginine supplementation improves the survival of virus-specific CD8⁺ T cells during <i>in vitro</i> expansion.","authors":"Takahiro Tomoda, Ai Kawana-Tachikawa, Shigeomi Shimizu, Satoshi Takahashi, Hirokazu Kanegane, Takahiro Kamiya, Kumi Inoue, Masatoshi Takagi, Tomohiro Morio","doi":"10.1093/immadv/ltag014","DOIUrl":"https://doi.org/10.1093/immadv/ltag014","url":null,"abstract":"<p><strong>Introduction: </strong>Virus-specific T cell therapy is a promising treatment for life-threatening viral infections following allogeneic hematopoietic stem cell transplantation. However, its efficacy is limited by apoptotic cell loss during <i>in vitro</i> expansion and the cryopreservation process.</p><p><strong>Materials and methods: </strong>Human virus-specific T cells were expanded <i>in vitro</i> with interleukin-7 and interleukin-15 in RPMI 1640-based medium with or without L-arginine supplementation, and their survival, phenotype, mitochondrial function, and cytokine signaling were evaluated.</p><p><strong>Results: </strong>Supplementation of the culture medium with L-arginine enhanced the survival of human virus-specific T cells during <i>in vitro</i> expansion. Supplementation of the RPMI 1640-based culture medium with L-arginine reduced apoptosis and was accompanied by increased expression of the anti-apoptotic protein MCL-1 in virus-specific CD8⁺ T cells. In parallel, modest differences in exhaustion- and differentiation-associated markers were observed. Consistent with these survival-associated changes, preservation of mitochondrial membrane potential was concurrently observed in non-apoptotic CD8⁺ T cells. Among several culture-associated factors that may contribute to mitochondrial preservation, L-arginine availability was associated, at least in part, with common gamma-chain cytokine-induced phosphorylation of mammalian target of rapamycin signalling and signal transducer and activator of transcription 5 downstream of interleukin-7 and interleukin-15 during <i>in vitro</i> culture.</p><p><strong>Conclusion: </strong>Together, these findings support L-arginine supplementation as a simple and clinically applicable strategy to enhance the durability of virus-specific T cell products during <i>in vitro</i> expansion, as well as cryopreservation and thawing.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"6 1","pages":"ltag014"},"PeriodicalIF":4.4,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992744","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":"ImmTACs overcome cytotoxic T cell suppression.","authors":"Lan Huynh, Abdullah Aljohani, Amal Alsubaiti, Tressan Grant, Alexandra Chapman, Gwilym Phillips, Jonathan Chamberlain, Alice Hayward-Wills, Ute Jungwirth, Mariolina Salio, Christopher J Holland, Christoph Wülfing","doi":"10.1093/immadv/ltag020","DOIUrl":"10.1093/immadv/ltag020","url":null,"abstract":"<p><strong>Introduction: </strong>Synthetic T cell receptor (TCR) engagers are cancer therapeutics that activate T cells through recognition of antigens on the tumor cell surface. Immune-mobilizing monoclonal TCRs against cancer (ImmTAC) are composed of the extracellular domains of the alpha and beta chains of an affinity-enhanced TCR recognizing a tumor-associated antigenic peptide-major histocompatibility complex (MHC) complex linked to an scFv fragment of an antibody against CD3ε. A first-in-class ImmTAC, Tebentafusp, is approved for the treatment of metastatic uveal melanoma. Here we asked how ImmTACs activate human primary cytotoxic T lymphocytes (CTL) in response to antigen-presenting tumor target cells.</p><p><strong>Materials and methods: </strong>We used a recently established experimental strategy to generate active and matched suppressed CTL <i>in vitro</i>.</p><p><strong>Results: </strong>ImmTACs could elicit tumor cell cytolysis in response to endogenous antigen presentation by both active and suppressed CTL, but much less so for IFNγ secretion, in a manner dependent on the engager affinity for CD3ε. ImmTACs did so by enhancing the efficient execution of subcellular CTL polarization steps required for effective cytolysis and could trigger calcium signaling.</p><p><strong>Conclusion: </strong>These data establish that ImmTACs are powerful inducers of CTL cytotoxicity and do so with a comparable efficacy and mechanism as direct engagement of a TCR by peptide-MHC. ImmTACs retain this capability under suppressive conditions comparable to those in the tumor microenvironment.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"6 1","pages":"ltag020"},"PeriodicalIF":4.4,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13593617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026956","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":"IVIG-associated anterior uveitis resolving after switch to subcutaneous immunoglobulin.","authors":"Vered Schichter Konfino, Oded Shamriz","doi":"10.1093/immadv/ltag018","DOIUrl":"10.1093/immadv/ltag018","url":null,"abstract":"<p><strong>Introduction: </strong>Intravenous immunoglobulin (IVIG) therapy can occasionally induce unexpected inflammatory complications.</p><p><strong>Materials and methods: </strong>A case report and literature review.</p><p><strong>Results: </strong>We report a patient with hypogammaglobulinemia and systemic autoimmunity who developed reproducible unilateral anterior uveitis following IVIG administration across multiple formulations. Discontinuation of IVIG resolved the ocular inflammation but caused underlying disease exacerbation. Transition to facilitated subcutaneous immunoglobulin (SCIG) achieved stable serum IgG levels and maintained complete ocular and systemic remission over a four-year follow-up period.</p><p><strong>Conclusion: </strong>This case demonstrates peak-driven immune activation as a plausible mechanism for IVIG-induced uveitis and highlights SCIG as a safe, effective therapeutic alternative that bypasses rapid peak IgG dynamics while preserving immune protection.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"6 1","pages":"ltag018"},"PeriodicalIF":4.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13511136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148835381","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":"Safety and efficacy of PRaG therapy in elderly cancer patients.","authors":"Xiangrong Zhao, MengMeng Yang, Junjun Zhang, Yuehong Kong, Meiling Xu, Rongzheng Chen, Qian Yin, Pengfei Xing, Liyuan Zhang","doi":"10.1093/immadv/ltag019","DOIUrl":"10.1093/immadv/ltag019","url":null,"abstract":"<p><strong>Introduction: </strong>PD-1/PD-L1 inhibitors lack evidence-based support in patients aged ≥75 years due to their frequent exclusion from clinical trials. This study aimed to evaluate the safety and efficacy of PRaG therapy-combining PD-1/PD-L1 inhibitors with radiotherapy-specifically in this elderly demographic.</p><p><strong>Materials and methods: </strong>Data were collected from patients aged ≥75 years who received PRaG therapy at our center between 1 January 2019, and 31 December 2024. Eligible patients were required to have at least one post-baseline efficacy evaluation. Tumor response was evaluated according to RECIST v1.1, and adverse events were graded using CTCAE v5.0.</p><p><strong>Results: </strong>A total of 36 elderly patients aged ≥75 years were included, with a median age of 77 years (range: 75-93). The objective response rate (ORR) was 23.5%, and the disease control rate (DCR) was 70.6%. After a median follow-up of 46.3 months, the median progression-free survival (mPFS) was 7.0 months (95% CI: 2.4-11.6 months) and the median overall survival (mOS) was 11.1 months (95% CI: 5.3-16.9 months). The Geriatric Nutritional Risk Index (GNRI) was associated with the efficacy of PRaG therapy, as well as PFS and OS. Any-grade treatment-related adverse events (TRAEs) occurred in 34 patients (94.4%), with 3 patients (8.3%) experiencing ≥Grade 3 TRAEs. No Grade 5 TRAEs were observed.</p><p><strong>Conclusion: </strong>The PRaG regimen appears feasible and tolerable in selected elderly patients with advanced cancer. Given the retrospective nature of this small cohort, an ongoing prospective trial (NCT06112041) will further validate these findings. Combining PRaG with robust nutritional support represents a rational hypothesis for future investigation.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"6 1","pages":"ltag019"},"PeriodicalIF":4.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889417","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":"Radiation resistance is a property of long-lived plasma cells but not their precursors.","authors":"Rosela H Webster, Alexandra R Dvorscek, Zhoujie Ding, David M Tarlinton, Marcus J Robinson","doi":"10.1093/immadv/ltag016","DOIUrl":"10.1093/immadv/ltag016","url":null,"abstract":"<p><strong>Introduction: </strong>Irradiation and reconstitution has often been used to analyze plasma cell turnover. Here, we characterized the kinetics of plasma cell reconstitution following irradiation, focusing on representation of recipient and donor plasma cells.</p><p><strong>Materials and methods: </strong>In a first setup, bone marrow chimeras were generated using congenic Ly5 allotype marked bone marrow transfer after lethal X-ray irradiation. Representation of donor and recipient B cells and plasma cells were tracked in the weeks thereafter. In a second setup, we repeated the reconstitution using plasma cell timestamp mice as recipients and BLIMP1^gfp as donor bone marrow, allowing tracing of both recipient- and donor-source plasma cells with fluorescent reporters.</p><p><strong>Results: </strong>In recipient spleen and bone marrow in the first setup, B cell and plasma cell numbers returned to homeostasis within 4 weeks of reconstitution. We determined that while B cells were essentially donor-derived by 4 weeks and plasma cells reached maximum donor representation at 4 weeks, they retained a significant fraction of recipient origin plasma cells to at least 8 weeks, the experiment endpoint. This clearly resolved plasma cell origin and revealed recipient plasma cells comprised both persistent and newly formed, the latter being the majority. When irradiated, timestamped mice were reconstituted with B-cell-insufficient µMT bone marrow, leaving irradiated recipient B cells as the sole source of new plasma cells, the recipients generated significantly more nascent plasma cells from endogenous B cells than occurred in the BLIMP1^gfp recipients.</p><p><strong>Conclusion: </strong>These data suggest that irradiated B cells are at a disadvantage to donor-derived B cells but can give rise to plasma cells when competition is alleviated, here by donor B-cell lymphopenia. Bone marrow reconstitution after irradiation thus reveals a population of radiation resistant long-lived plasma cells and B cell or early-stage plasma cell competition for production and retention.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"6 1","pages":"ltag016"},"PeriodicalIF":4.4,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018990","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 of proton-pump inhibitor and anti-CD3 F(ab')₂ for islet neogenesis and immune modulation in type 1 diabetes.","authors":"Tung-Yun Wu, Che-Yi Chen, Michael Chen, Chang-Hung Wang, An-Pei Kao, Kai-Hung Wang, Kuo-Hsiang Chuang, Shyr-Yi Lin","doi":"10.1093/immadv/ltag017","DOIUrl":"10.1093/immadv/ltag017","url":null,"abstract":"<p><strong>Introduction: </strong>Type 1 diabetes (T1D) is an autoimmune disease characterized by T cell-mediated destruction of pancreatic β cells. Current insulin therapy does not address autoimmune pathology or restore endogenous β-cell function, highlighting the need for disease-modifying strategies.</p><p><strong>Methods: </strong>We developed a combination therapy integrating a proton pump inhibitor (PPI; omeprazole) with a non-Fc-binding anti-CD3 F(ab')₂ antibody fragment (anti-CD3 F(ab')₂) to concurrently promote β-cell neogenesis and modulate autoimmune T-cell responses. T1D was induced in nonobese diabetic (NOD) mice using a cyclophosphamide-accelerated protocol (CY-NOD). Following hyperglycemia onset, mice received combination treatment and were evaluated by blood glucose monitoring, flow cytometric analysis of T-cell populations, and assessment of pancreatic β-cell function. Therapeutic efficacy was further examined in spontaneous-onset NOD mice.</p><p><strong>Results: </strong>Combination therapy restored normoglycemia without exogenous insulin, reduced lymphocytic infiltration in pancreatic islets, and preserved endogenous insulin secretion. Treatment decreased pathogenic CD4⁺ and CD8⁺ T cells, increased regulatory T cells, and enhanced transforming growth factor-β expression. Comparable and durable glycemic control was observed in spontaneous-onset NOD mice.</p><p><strong>Conclusions: </strong>Concurrent modulation of β-cell function and autoimmune immunity achieved sustained glycemic control in T1D models. The use of clinically approved agents supports the translational potential of this non-insulin-dependent therapeutic strategy.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"6 1","pages":"ltag017"},"PeriodicalIF":4.4,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13426313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148654831","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":"Growth factor supportive care for chemotherapy-induced neutropenia suppresses antitumour immunity in checkpoint blockade-responsive pancreatic cancer.","authors":"Brendan D Parent, Anthony E Kelly, Megan T Hoffman, Michael Dougan, Andrew J Aguirre, Stephanie K Dougan","doi":"10.1093/immadv/ltag013","DOIUrl":"10.1093/immadv/ltag013","url":null,"abstract":"<p><strong>Introduction: </strong>Growth factors, including granulocyte colony-stimulating factor (G-CSF; pegfilgrastim, filgrastim), are used for prophylaxis or treatment of chemotherapy-induced neutropenia, yet their effects on antitumour immunity remain incompletely understood. We previously found that serum from patients with pancreatic ductal adenocarcinoma (PDAC) treated with multiagent chemotherapy plus G-CSF drove differentiation of T cell-suppressive monocytes <i>in vitro</i>, suggesting that supportive care interventions may shape immune responses in this disease.</p><p><strong>Methods: </strong>We evaluated the immunologic and therapeutic impact of G-CSF in two murine PDAC models that differ in their baseline frequencies of infiltrating T cells and in their responsiveness to checkpoint blockade immunotherapy.</p><p><strong>Results: </strong>In poorly immunogenic, T-cell-low tumours, use of G-CSF did not affect tumour growth or response to chemo- or immunotherapy, although neutrophil recovery was improved in mice receiving FOLFIRINOX and G-CSF compared to chemotherapy alone. In immunogenic tumours with a robust endogenous T-cell response, combination anti-PD1 and anti-CTLA-4 therapy resulted in durable tumour clearance. Combination with G-CSF diminished the effectiveness of checkpoint blockade and resulted in significantly fewer cured mice.</p><p><strong>Conclusion: </strong>G-CSF, commonly used for supportive care with FOLFIRINOX and other chemotherapy regimens, induces systemic immune suppression that can reduce the efficacy of T-cell-targeting immunotherapies.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"6 1","pages":"ltag013"},"PeriodicalIF":4.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148586175","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":"Harnessing the duality of regulatory B cells: from identification of characteristic molecules to therapeutic targeting.","authors":"Luman Wang, Ronghua Liu, Yiwei Chu","doi":"10.1093/immadv/ltag011","DOIUrl":"10.1093/immadv/ltag011","url":null,"abstract":"<p><p>The field of immunology is increasingly intersecting with molecular biology, metabolic biology, and neurobiology (Zhu et al, A neuroimmune circuit mediates cancer cachexia-associated apathy. <i>Science</i> 2025;388:eadm8857; Jaschke et al, Gut-to-brain signaling restricts dietary protein intake during recovery from catabolic states. <i>Cell</i> 2025;188:7481-7494.e16; Zheremyan et al, Regulatory B cells: changing the landscape of immunoregulation and immunotherapy. <i>Cytokine Growth Factor Rev</i> 2025;86:121-36), marking a shift beyond traditional research approaches toward a more comprehensive understanding of the immune system. Central to this integrated perspective is the growing recognition that B cells are not only antibody producers, but also multifunctional cells dynamically modulated by their microenvironment. This comprehensive synthesis of recent research illuminates the dual nature of regulatory B cells (Bregs) as pivotal orchestrators of immune homeostasis. We examine how Bregs, governed by complex metabolic cues, neural signaling pathways, and local tissue microenvironments, can either suppress pathological inflammation or be co-opted to drive disease progression in autoimmunity, cancer, and allergic conditions. Understanding these microenvironmental determinants of Breg function is particularly critical for developing next-generation prognostic tools and targeted therapeutic strategies that effectively modulate B cell activity in various disease states.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"6 1","pages":"ltag011"},"PeriodicalIF":4.4,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148439227","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":"Vaccination against tumour endothelial marker Robo4 inhibits tumour growth.","authors":"Fernanda Escobar-Riquelme, Muhammet Ali Kara, Michael J Price, Angela Hidalgo-Gajardo, Hayley L Carr, David Bending, Roy Bicknell, Natalia Savelyeva, Kai-Michael Toellner, Yang Zhang","doi":"10.1093/immadv/ltag005","DOIUrl":"10.1093/immadv/ltag005","url":null,"abstract":"<p><strong>Introduction: </strong>Targeting tumour antigens is a major challenge in cancer-immunotherapy. We use active vaccination to induce antibodies targeting self-antigen Robo4, which is selectively expressed on tumour vascular endothelium, and supports vascular development. Our previous work showed that a conjugate of Robo4 with a foreign carrier protein induced autoantibodies specific to Robo4, which inhibited angiogenesis and tumour growth.</p><p><strong>Methods: </strong>To translate the vaccine protocol to exploit a carrier protein used in routine human vaccination schedules, the well-characterized, non-toxic fragment C of tetanus toxin (TTc) was selected as the carrier protein. Recombinant protein Robo4-TTc (R4-TTc) was produced by Robo4 genetically linked to TTc.</p><p><strong>Results: </strong>Priming with the carrier TTc followed by boost with Robo4-TTc (R4-TTc) efficiently induces strong antibody responses to Robo4 and inhibits tumour growth in LLC1 and 4T1 tumour models. The growth inhibition was correlated with anti-Robo4 IgG1 titres. Furthermore, decreased vessel formation and increased immune cell infiltration in tumours from R4-TTc vaccinated mice in the absence of detectable adverse effects on health.</p><p><strong>Conclusion: </strong>The data indicate that this vaccination strategy remodels tumour vessels and probably promotes immunogenic pathway activation, therefore repressing tumour growth.</p>","PeriodicalId":73353,"journal":{"name":"Immunotherapy advances","volume":"6 1","pages":"ltag005"},"PeriodicalIF":4.4,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13296997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148347694","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}