{"title":"Cross-organ hierarchy of HLA molecular mismatches in donor-specific antibody development in solid organ transplantations.","authors":"Masaaki Hirata, Kazuto Tsukita, Takero Shindo, Shintaro Yagi, Takashi Ito, Satona Tanaka, Ryo Fujimoto, Hidenao Kayawake, Kenji Nakamura, Nobuhiro Fujiyama, Mitsuru Saito, Kimiko Yurugi, Rie Hishida, Arisa Kato, Atsushi Kawaguchi, Tomonori Habuchi, Takashi Kobayashi, Hiroshi Date, Etsuro Hatano","doi":"10.1016/j.xcrm.2025.102153","DOIUrl":"10.1016/j.xcrm.2025.102153","url":null,"abstract":"<p><p>Donor-specific antibodies (DSAs) against human leukocyte antigen (HLA) play a crucial role in antibody-mediated rejection, a major barrier to successful organ transplantation. Donor-recipient HLA molecular incompatibility critically influences DSA susceptibility, commonly assessed by analyzing mismatches in the HLA eplet repertoire. This study, including six distinct liver, lung, and kidney transplant cohorts from two centers (978 donor-recipient pairs), explores associations between individual eplet mismatches and DSA development. Certain mismatched eplets are strongly linked to DSA development, while others show weaker associations, a trend consistent across different organ types. Machine learning leverages these hierarchical associations to develop an eplet risk score (ERS), outperforming traditional eplet mismatch assessments. Furthermore, T cell proliferation in mixed lymphocyte reaction in vitro correlates with the ERS, attenuated by antibody-mediated inhibition of a mismatched DSA-associated eplet. These results establish the differential immunological impacts of mismatched HLA eplets as integral in clinical practice and therapeutic innovation.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102153"},"PeriodicalIF":11.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell Reports MedicinePub Date : 2025-06-17Epub Date: 2025-06-03DOI: 10.1016/j.xcrm.2025.102160
Anthony Tighe, Louisa Nelson, Robert D Morgan, Bethany M Barnes, I-Hsuan Lin, Samantha Littler, James Altringham, Jean Ling Tan, Joanne C McGrail, Stephen S Taylor
{"title":"Screening a living biobank identifies cabazitaxel as a strategy to combat acquired taxol resistance in high-grade serous ovarian cancer.","authors":"Anthony Tighe, Louisa Nelson, Robert D Morgan, Bethany M Barnes, I-Hsuan Lin, Samantha Littler, James Altringham, Jean Ling Tan, Joanne C McGrail, Stephen S Taylor","doi":"10.1016/j.xcrm.2025.102160","DOIUrl":"10.1016/j.xcrm.2025.102160","url":null,"abstract":"<p><p>The anti-mitotic agent taxol (paclitaxel) remains a cornerstone of ovarian cancer treatment. To tackle drug resistance and toxicity, second-generation targeted anti-mitotic agents and combination strategies are being explored but have yet to demonstrate meaningful clinical benefits. A limitation is the lack of a platform to compare strategies in models that capture disease heterogeneity. To overcome this, we screen 83 patient-derived ex vivo ovarian cancer models that exhibit extensive intra- and inter-patient heterogeneity, testing four distinct approaches to enhance taxol sensitivity. Inhibitors of the HSET kinesin or the Mps1 spindle assembly checkpoint kinase show minimal impact on the taxol sensitivity landscape. By contrast, Bcl-xL inhibition exerts a global anti-proliferative effect. Inhibition of the MDR1 drug efflux pump restores taxol sensitivity in models characterized by ABCB1 overexpression. These MDR1-driven resistant models also respond to cabazitaxel, which is a poor MDR1 substrate, highlighting a potential therapeutic option for ovarian cancers with acquired taxol resistance.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102160"},"PeriodicalIF":11.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bi-Huei Yang, Alma Gutierrez, Angela Liao, Soheila Shirinbak, Bjoern Gaertner, Mochtar Pribadi, Hui-Yi Chu, Pei-Fang Tsai, Yu-Sheng Eason Lin, David Gonzalez, Wen-I Yeh, Chia-Wei Chang, Ryan Bjordahl, Tom Lee, Martin Hosking, Eigen Peralta, Bahram Valamehr
{"title":"iPSC-derived trimodal T cells engineered with CAR, TCR, and hnCD16 modalities can overcome antigen escape in heterogeneous tumors.","authors":"Bi-Huei Yang, Alma Gutierrez, Angela Liao, Soheila Shirinbak, Bjoern Gaertner, Mochtar Pribadi, Hui-Yi Chu, Pei-Fang Tsai, Yu-Sheng Eason Lin, David Gonzalez, Wen-I Yeh, Chia-Wei Chang, Ryan Bjordahl, Tom Lee, Martin Hosking, Eigen Peralta, Bahram Valamehr","doi":"10.1016/j.xcrm.2025.102195","DOIUrl":"10.1016/j.xcrm.2025.102195","url":null,"abstract":"<p><p>Although chimeric antigen receptor (CAR) T cells have demonstrated therapeutic activity in hematopoietic malignancies, tumor heterogeneity has impeded the efficacy of CAR T cells and their extension into successful solid tumor treatment. To address these challenges, induced pluripotent stem cell (iPSC)-derived T (iT) cells are engineered to uniformly express CAR and T cell receptor (TCR), enabling targeting of both surface and intracellular antigens, respectively, along with a high-affinity, non-cleavable variant of CD16a (hnCD16) to support antibody-dependent cellular cytotoxicity (ADCC) when combined with therapeutic antibodies. Co-expression of each antitumor strategy on engineered iT cells enables independent and antigen-specific targeting across a diverse set of liquid and solid tumors. In heterogeneous tumor models, coactivation of these modalities is required for measurable antitumor efficacy, with activation of all three modalities displaying maximal efficacy. These data highlight the therapeutic potential of an off-the-shelf engineered iPSC-derived trimodal T cell expressing CAR, TCR, and hnCD16 to combat difficult-to-treat heterogeneous tumors.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102195"},"PeriodicalIF":11.7,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuqing Zhang, Zehua Li, Jessica Ritter, Elliott J Brea, Navin R Mahadevan, Deborah A Dillon, Sung-Rye Park, Eric Minwei Liu, Michael Y Tolstorukov, William E McGourty, Patrick Lizotte, Elena V Ivanova, Caroline Fahey, Koji Haratani, Tran C Thai, Kara M Soroko, Sophie Kivlehan, Eric L Smith, Prafulla C Gokhale, Cloud P Paweletz, David A Barbie, Thanh U Barbie
{"title":"Immune targeting of triple-negative breast cancer through a clinically actionable STING agonist-CAR T cell platform.","authors":"Yuqing Zhang, Zehua Li, Jessica Ritter, Elliott J Brea, Navin R Mahadevan, Deborah A Dillon, Sung-Rye Park, Eric Minwei Liu, Michael Y Tolstorukov, William E McGourty, Patrick Lizotte, Elena V Ivanova, Caroline Fahey, Koji Haratani, Tran C Thai, Kara M Soroko, Sophie Kivlehan, Eric L Smith, Prafulla C Gokhale, Cloud P Paweletz, David A Barbie, Thanh U Barbie","doi":"10.1016/j.xcrm.2025.102198","DOIUrl":"10.1016/j.xcrm.2025.102198","url":null,"abstract":"<p><p>Stimulator of interferon genes (STING) has emerged as a critical cancer immunotherapy target. However, no STING agonist has advanced beyond phase I/II clinical trials, as obstacles center around applying STING agonism to the appropriate clinical context, retaining it in the tumor microenvironment (TME), and limiting its T cell toxicity. Using triple-negative breast cancer (TNBC), we identify defective STING turnover as a cancer state promoting hypersensitivity to STING agonism. We also repurpose a US Food and Drug Administration (FDA)-approved polyethylene glycol (PEG) biopsy marker to deliver STING agonists in a controlled release fashion into the TME. However, STING agonist-induced T cell toxicity limits robust endogenous clonal T cell response, which can be overcome by sequential co-delivery of the STING agonists with CAR T cell therapy using the same PEG marker, eradicating orthotopic TNBC in mouse models while also controlling distant disease. These findings identify a highly translatable platform to combine STING agonists with CAR T cell therapy locally for TNBC and potentially other solid cancers.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102198"},"PeriodicalIF":11.7,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Raúl Del Rey-Vergara, Miguel Alejandro Galindo-Campos, Pedro Rocha, Marina Carpes, Carlos Martínez, Laura Masfarré, Silvia Menéndez, Fabricio Quimis, Adrià Rossell, Albert Iñañez, Sandra Pérez-Buira, Federico Rojo, Ramon Gimeno, Dolores Isla, Jon Zugazagoitia, Cristina Martí Blanco, Rosario García-Campelo, Alberto Moreno-Vega, Luis León-Mateos, Ángel Callejo Mellén, Kwon-Sik Park, Simon Heeke, John V Heymach, Álvaro Taus, Luis Paz-Ares, Ana Rovira, Edurne Arriola
{"title":"MET pathway inhibition increases chemo-immunotherapy efficacy in small cell lung cancer.","authors":"Raúl Del Rey-Vergara, Miguel Alejandro Galindo-Campos, Pedro Rocha, Marina Carpes, Carlos Martínez, Laura Masfarré, Silvia Menéndez, Fabricio Quimis, Adrià Rossell, Albert Iñañez, Sandra Pérez-Buira, Federico Rojo, Ramon Gimeno, Dolores Isla, Jon Zugazagoitia, Cristina Martí Blanco, Rosario García-Campelo, Alberto Moreno-Vega, Luis León-Mateos, Ángel Callejo Mellén, Kwon-Sik Park, Simon Heeke, John V Heymach, Álvaro Taus, Luis Paz-Ares, Ana Rovira, Edurne Arriola","doi":"10.1016/j.xcrm.2025.102194","DOIUrl":"10.1016/j.xcrm.2025.102194","url":null,"abstract":"<p><p>The introduction of immunotherapy as a first-line treatment for advanced small cell lung cancer (SCLC) represents significant progress, yet there remains an opportunity to further improve patient outcomes. Hepatocyte growth factor (HGF) receptor (MET) pathway activation promotes epithelial-mesenchymal transition, driving chemoresistance and potentially impairing the efficacy of immunotherapy. In SCLC mouse models, adding MET inhibition to chemo-immunotherapy (anti-PD-L1) reduces tumor growth, extends survival, and reshapes the tumor microenvironment by decreasing suppressive myeloid cell infiltration and enhancing the immune response. Analysis of pretreatment human SCLC tumor samples reveals that myeloid-enriched immune infiltrates may contribute to chemo-immunotherapy resistance. Elevated serum HGF levels are associated with a mesenchymal and inflamed phenotype, suggesting that patients with these characteristics might benefit from MET inhibitor-based therapeutic strategies. These findings provide strong preclinical and translational evidence supporting MET inhibition as a therapeutic approach to overcome treatment resistance, enhancing the immune response and improving outcomes in biomarker-defined subsets of SCLC patients.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102194"},"PeriodicalIF":11.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liulu Zhang, Lu Yang, Yan Ge, Zhaowen Zhu, Bo Chen, Ciqiu Yang, Hongfei Gao, Mei Yang, Teng Zhu, Kun Wang
{"title":"Neoadjuvant anlotinib/sintilimab plus chemotherapy in triple-negative breast cancer (NeoSACT): Phase 2 trial.","authors":"Liulu Zhang, Lu Yang, Yan Ge, Zhaowen Zhu, Bo Chen, Ciqiu Yang, Hongfei Gao, Mei Yang, Teng Zhu, Kun Wang","doi":"10.1016/j.xcrm.2025.102193","DOIUrl":"10.1016/j.xcrm.2025.102193","url":null,"abstract":"<p><p>Tumor angiogenesis contributes to immune evasion, and vascular normalization enhances immunotherapy response by reshaping the tumor microenvironment. This phase 2 trial evaluates neoadjuvant anlotinib (antiangiogenic), sintilimab (programmed cell death protein 1 [PD-1] inhibitor), and chemotherapy in 29 patients with stage II-III triple-negative breast cancer (TNBC). The primary endpoint, pathological complete response (pCR), is achieved in 69.0% (95% confidence interval [CI]: 49.0%-85.0%), with an 86.2% minimal residual disease (residual cancer burden [RCB] 0 + 1) rate. Notably, programmed death-ligand 1 (PD-L1)-negative patients achieve a 75.0% pCR rate, comparable to PD-L1-positive patients (64.7%). The 2-year event-free survival (EFS) is 92.4%, with 100% EFS in pCR patients. Grade 3/4 adverse events occur in 31.0% of patients, primarily rash and hematologic toxicities. These results demonstrate that combining antiangiogenic therapy with immunotherapy and chemotherapy enhances treatment efficacy, potentially overcoming PD-L1 limitations, and supports further investigation in high-risk TNBC. This trial was registered at ClinicalTrials.gov (NCT04877821).</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102193"},"PeriodicalIF":11.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Taylon F Silva, Elizabeth Hutchins, Wenyan Zhao, Yari Ciani, Minhyung Kim, Emily Ko, Javier Mariscal, Zhuyu Qiu, Fatima Bedier, Agnes Kittel, Bo Zhou, Yang Wang, Megan Hall, Francesca Galasso, Rebecca Reiman, Michael R Freeman, Sarah Parker, Jennifer Van Eyk, Wei Yang, Edwin Posadas, Jlenia Guarnerio, John Nolan, Clotilde Théry, Andries Zijlstra, Shannon Stott, Sungyong You, Francesca Demichelis, Paul C Boutros, Kendall Van Keuren-Jensen, Dolores Di Vizio
{"title":"Extracellular vesicle heterogeneity through the lens of multiomics.","authors":"Taylon F Silva, Elizabeth Hutchins, Wenyan Zhao, Yari Ciani, Minhyung Kim, Emily Ko, Javier Mariscal, Zhuyu Qiu, Fatima Bedier, Agnes Kittel, Bo Zhou, Yang Wang, Megan Hall, Francesca Galasso, Rebecca Reiman, Michael R Freeman, Sarah Parker, Jennifer Van Eyk, Wei Yang, Edwin Posadas, Jlenia Guarnerio, John Nolan, Clotilde Théry, Andries Zijlstra, Shannon Stott, Sungyong You, Francesca Demichelis, Paul C Boutros, Kendall Van Keuren-Jensen, Dolores Di Vizio","doi":"10.1016/j.xcrm.2025.102161","DOIUrl":"10.1016/j.xcrm.2025.102161","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are heterogeneous in size, biogenesis, content, and function. Aggressive cancer cells release a distinct, poorly characterized, and particularly large EV subtype, namely large oncosomes (LOs). This study employs an optimized method to improve LO yields and integrates mass spectrometry and RNA sequencing (RNA-seq) to profile their molecular cargo. A consistent set of proteins enriched in LOs is identified across glioma, prostate, and breast cancer cell lines. These proteins are also present as mRNA in LOs from the prostate cancer model and are abundant in plasma LOs from 20 patients with metastasis. Single-LO RNA-seq confirms bulk LO cargo, demonstrating the utility of single-cell technologies for large vesicle analysis. Our patient study provides proof-of-principle evidence that we can use multiomics to delve into EV heterogeneity, biogenesis, and composition. It also suggests that plasma LOs help stratify patients, supporting their potential prognostic value for developing a multi-analyte approach for liquid biopsy.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102161"},"PeriodicalIF":11.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah Naomi Olsen, Bryn Anderson, Charlie Hatton, Zhengtao Chu, Christopher Simpkins, Yanhe Wen, Wallace Bourgeois, Elena L Haarer, Myles Brown, Rinath Jeselsohn, Alana L Welm, Eneda Toska, Scott A Armstrong
{"title":"Combined inhibition of KAT6A/B and Menin reverses estrogen receptor-driven gene expression programs in breast cancer.","authors":"Sarah Naomi Olsen, Bryn Anderson, Charlie Hatton, Zhengtao Chu, Christopher Simpkins, Yanhe Wen, Wallace Bourgeois, Elena L Haarer, Myles Brown, Rinath Jeselsohn, Alana L Welm, Eneda Toska, Scott A Armstrong","doi":"10.1016/j.xcrm.2025.102192","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.102192","url":null,"abstract":"<p><p>KAT6A is a histone acetyltransferase that is emerging as a therapeutic target in cancer, including estrogen receptor-positive (ER+) breast cancer. Here, we perform CRISPR screens to identify the chromatin adaptor Menin as a regulator of KAT6A/B inhibitor response. Co-treatment with KAT6A/B and Menin inhibitors has synergistic anti-proliferative effects in ER+, but not ER-, breast cancer lines. Our data reveal that KAT6A and Menin-KMT2A cooperatively regulate ER-driven gene expression via direct effects on ESR1 expression and co-localization at ER target genes. Combined KAT6A/B and Menin inhibition displaces KAT6A and Menin-KMT2A from promoters of ER-driven genes leading to selective RNA polymerase II chromatin loss at these loci. Importantly, combined KAT6A/B and Menin inhibition is effective in ER+ patient-derived xenograft models and in multiple models of endocrine resistance. KAT6A/B and Menin inhibitors are currently in clinical trials and have shown manageable toxicity profiles, underscoring the potential therapeutic relevance for ER+ breast cancer.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102192"},"PeriodicalIF":11.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Felicia Pagliuca.","authors":"Felicia Pagliuca","doi":"10.1016/j.xcrm.2025.102142","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.102142","url":null,"abstract":"<p><p>Dr. Felicia Pagliuca is currently Senior Vice President, Cell and Genetic Therapy Research at Vertex Pharmaceuticals. She received a BS from Duke University and a PhD from Cambridge University where she was a Marshall Scholar. She completed her postdoctoral fellowship with Dr. Douglas Melton at the Harvard Stem Cell Institute, where she worked with Dr. Melton to discover how to generate stem cell-derived pancreatic beta cells in the lab. She co-founded Semma Therapeutics with Dr. Melton in 2014. While at Semma, she served as Vice President of Cell Biology Research and Development, where she led the development of investigational cell therapies for the treatment of type 1 diabetes. She joined Vertex Pharmaceuticals in 2019, when Semma was acquired by Vertex, and served as the company's Vice President and Disease Area Executive for type 1 diabetes for 5 years before moving into her current role.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":"6 5","pages":"102142"},"PeriodicalIF":11.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell Reports MedicinePub Date : 2025-05-20Epub Date: 2025-05-08DOI: 10.1016/j.xcrm.2025.102092
Cheng Gao, Ruifeng Luo, Cheryl H T Kwong, Jinwei Liu, Mian Tang, Beibei Xie, Tianshun Duan, Ruibing Wang
{"title":"Cancer vaccine from intracellularly gelated tumor cells functionalized with CD47 blockage and damage-associated molecular pattern exposure.","authors":"Cheng Gao, Ruifeng Luo, Cheryl H T Kwong, Jinwei Liu, Mian Tang, Beibei Xie, Tianshun Duan, Ruibing Wang","doi":"10.1016/j.xcrm.2025.102092","DOIUrl":"10.1016/j.xcrm.2025.102092","url":null,"abstract":"<p><p>The effectiveness of whole tumor cell vaccines prepared by traditional inactivation methodology is often hindered by insufficient immunogenicity. Here, we report development of a cancer vaccine through the intracellular gelation of tumor cells, combined with CD47 blockade and damage-associated molecular pattern (DAMP) exposure, for effective tumor prevention and treatment. Intracellular hydrogelation preserves the morphology and antigenicity of tumor cells. CD47 blockade and DAMP exposure synergistically enhance the \"eat me\" signals and inhibit the \"don't eat me\" signals on tumor cells, significantly improving their immunogenicity. In the context of tumor prevention and treatment of pre-existing tumors, this vaccine polarizes CD4<sup>+</sup> T cells toward a T<sub>H</sub>1 phenotype, reduces regulatory T cells and T cell exhaustion, and elicits a robust tumor-antigen-specific T cell response. When combined with an immune checkpoint inhibitor, this vaccine demonstrates enhanced efficacy in eradicating established tumors. The successful application of this vaccine using ascites and subcutaneous tumor cells supports the feasibility of developing personalized whole tumor cell vaccines for diverse tumor types.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102092"},"PeriodicalIF":11.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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