Cancer immunology research最新文献

{"title":"Age-Associated Contraction of Tumor-Specific T Cells Impairs Antitumor Immunity.","authors":"Peter Georgiev, SeongJun Han, Amy Y Huang, Thao H Nguyen, Jefte M Drijvers, Hannah Creasey, Joseph A Pereira, Cong-Hui Yao, Joon Seok Park, Thomas S Conway, Megan E Fung, Dan Liang, Michael Peluso, Shakchhi Joshi, Jared H Rowe, Brian C Miller, Gordon J Freeman, Arlene H Sharpe, Marcia C Haigis, Alison E Ringel","doi":"10.1158/2326-6066.CIR-24-0463","DOIUrl":"10.1158/2326-6066.CIR-24-0463","url":null,"abstract":"<p><p>Progressive decline of the adaptive immune system with increasing age coincides with a sharp increase in cancer incidence. In this study, we set out to understand whether deficits in antitumor immunity with advanced age promote tumor progression and/or drive resistance to immunotherapy. We found that multiple syngeneic cancers grew more rapidly in aged versus young adult mice, driven by dysfunctional CD8+ T-cell responses. By systematically mapping immune cell profiles within tumors, we identified loss of tumor antigen-specific CD8+ T cells as a primary feature accelerating the growth of tumors in aged mice and driving resistance to immunotherapy. When antigen-specific T cells from young adult mice were administered to aged mice, tumor outgrowth was delayed and the aged animals became sensitive to PD-1 blockade. These studies reveal how age-associated CD8+ T-cell dysfunction may license tumorigenesis in elderly patients and have important implications for the use of aged mice as preclinical models of aging and cancer.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1525-1541"},"PeriodicalIF":8.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072106","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}

{"title":"Blocking CX3CR1+ Tumor-Associated Macrophages Enhances the Efficacy of Anti-PD1 Therapy in Hepatocellular Carcinoma.","authors":"Xiaonan Xiang, Kai Wang, Hui Zhang, Haibo Mou, Zhixiong Shi, Yaoye Tao, Hongliang Song, Zhengxing Lian, Shuai Wang, Di Lu, Xuyong Wei, Haiyang Xie, Shusen Zheng, Jianguo Wang, Xiao Xu","doi":"10.1158/2326-6066.CIR-23-0627","DOIUrl":"10.1158/2326-6066.CIR-23-0627","url":null,"abstract":"<p><p>The efficacy of immune checkpoint inhibitors in the treatment of hepatocellular carcinoma (HCC) remains limited, highlighting the need for further investigation into the mechanisms underlying treatment resistance. Accumulating evidence indicates that tumor-associated macrophages (TAM) within the tumor microenvironment demonstrate a key role in immune evasion and treatment resistance. This study explored the role of TAMs in the HCC tumor microenvironment. Our findings reveal that TAMs expressing CX3C motif chemokine receptor 1 (CX3CR1) induced T-cell exhaustion through IL27 secretion in orthotopic models of HCC following treatment with anti-PD1. Moreover, we identified prostaglandin E2 (PGE2), released by immune-attacked tumor cells, as a key regulator of TAM transition to a CX3CR1+ phenotype. To augment the therapeutic response to anti-PD1 therapy, we propose targeting CX3CR1+ TAMs in addition to anti-PD1 therapy. Our study contributes to the understanding of the role of TAMs in cancer immunotherapy and highlights potential clinical implications for HCC treatment. The combination of targeting CX3CR1+ TAMs with anti-PD1 therapy holds promise for enhancing the efficacy of immunotherapeutic interventions in patients with HCC.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1603-1620"},"PeriodicalIF":8.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901041","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":"The Spatial Structure of the Tumor Immune Microenvironment Can Explain and Predict Patient Response in High-Grade Serous Carcinoma.","authors":"Lucy B Van Kleunen, Mansooreh Ahmadian, Miriam D Post, Rebecca J Wolsky, Christian Rickert, Kimberly R Jordan, Junxiao Hu, Jennifer K Richer, Lindsay W Brubaker, Nicole Marjon, Kian Behbakht, Matthew J Sikora, Benjamin G Bitler, Aaron Clauset","doi":"10.1158/2326-6066.CIR-23-1109","DOIUrl":"10.1158/2326-6066.CIR-23-1109","url":null,"abstract":"<p><p>Ovarian cancer is the deadliest gynecologic malignancy, and therapeutic options and mortality rates over the last three decades have largely not changed. Recent studies indicate that the composition of the tumor immune microenvironment (TIME) influences patient outcomes. To improve spatial understanding of the TIME, we performed multiplexed ion beam imaging on 83 human high-grade serous carcinoma tumor samples, identifying approximately 160,000 cells across 23 cell types. From the 77 of these samples that met inclusion criteria, we generated composition features based on cell type proportions, spatial features based on the distances between cell types, and spatial network features representing cell interactions and cell clustering patterns, which we linked to traditional clinical and IHC variables and patient overall survival (OS) and progression-free survival (PFS) outcomes. Among these features, we found several significant univariate correlations, including B-cell contact with M1 macrophages (OS HR = 0.696; P = 0.011; PFS HR = 0.734; P = 0.039). We then used high-dimensional random forest models to evaluate out-of-sample predictive performance for OS and PFS outcomes and to derive relative feature importance scores for each feature. The top model for predicting low or high PFS used TIME composition and spatial features and achieved an average AUC score of 0.71. The results demonstrate the importance of spatial structure in understanding how the TIME contributes to treatment outcomes. Furthermore, the present study provides a generalizable roadmap for spatial analyses of the TIME in ovarian cancer research.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1492-1507"},"PeriodicalIF":8.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901042","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}

{"title":"Organ-Specific Immune Setpoints Underlie Divergent Immune Profiles across Metastatic Sites in Breast Cancer.","authors":"Colt A Egelston, Weihua Guo, Diana L Simons, Jian Ye, Christian Avalos, Shawn T Solomon, Mary Nwangwu, Michael S Nelson, Jiayi Tan, Eliza R Bacon, Kena Ihle, Daniel Schmolze, Lusine Tumyan, James R Waisman, Peter P Lee","doi":"10.1158/2326-6066.CIR-23-0718","DOIUrl":"10.1158/2326-6066.CIR-23-0718","url":null,"abstract":"<p><p>Immune composition within the tumor microenvironment (TME) plays a central role in the propensity of cancer cells to metastasize and respond to therapy. Previous studies have suggested that the metastatic TME is immune-suppressed. However, limited accessibility to multiple metastatic sites within patients has made assessing the immune TME difficult in the context of multiorgan metastases. We utilized a rapid postmortem tissue collection protocol to assess the immune composition of numerous sites of breast cancer metastasis and paired tumor-free tissues. Metastases had comparable immune cell densities and compositions to paired tumor-free tissues of the same organ type. In contrast, immune cell densities in both metastatic and tumor-free tissues differed significantly between organ types, with lung immune infiltration being consistently greater than that in the liver. These immune profiling results were consistent between flow cytometry and multiplex immunofluorescence-based spatial analysis. Furthermore, we found that granulocytes were the predominant tumor-infiltrating immune cells in lung and liver metastases, and these granulocytes comprised most PD-L1-expressing cells in many tissue sites. We also identified distinct potential mechanisms of immunosuppression in lung and liver metastases, with the lung having increased expression of PD-L1+ antigen-presenting cells and the liver having higher numbers of activated regulatory T cells and HLA-DRlow monocytes. Together, these results demonstrate that the immune contexture of metastases is dictated by organ type and that immunotherapy strategies may benefit from unique tailoring to the tissue-specific features of the immune TME.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1559-1573"},"PeriodicalIF":8.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757319","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}

{"title":"Tumor-Associated Antigen Burden Correlates with Immune Checkpoint Blockade Benefit in Tumors with Low Levels of T-cell Exhaustion.","authors":"Yue Wang, Mengying Hu, Olivera J Finn, Xiao-Song Wang","doi":"10.1158/2326-6066.CIR-23-0932","DOIUrl":"10.1158/2326-6066.CIR-23-0932","url":null,"abstract":"<p><p>Tumor-associated antigens (TAA) are important targets for cancer vaccines. However, TAA-based vaccines have not yet achieved their full potential in clinical trials. In contrast, immune checkpoint blockade (ICB) has emerged as an effective therapy, leading to durable responses in selected patients with cancer. To date, few generalizable associations between TAAs and ICB benefit have been reported, with most studies focusing on melanoma, which has the highest mutation rate in cancer. In this study, we developed a TAA burden (TAB) algorithm based on known and putative TAAs and investigated the association of TAB with ICB benefit. Analysis of the IMvigor210 patient cohort of urothelial carcinoma treated with anti-PDL1 revealed that high tumor mutation burden weakened the association of TAB with ICB benefit. Furthermore, TAB correlated with ICB efficacy in tumors characterized by negative PDL1 staining on immune cells; however, high levels of PDL1 staining on immune cells were linked to T-cell exhaustion. Validation across independent clinical datasets-including urothelial carcinoma cohorts treated with anti-PD1/PDL1 agents and neoadjuvant anti-PD1 trials for head and neck cancers-corroborated the finding that TAB correlates with ICB benefit in tumors with low T-cell exhaustion. Pan-cancer analyses revealed that in most cancer entities, tumors with higher T-cell exhaustion exhibited lower TAB levels, implying possible immunoediting of TAAs in tumors with established antitumor immunity. Our study challenges the prevailing notion of a lack of association between TAAs and ICB response. It also underscores the need for future investigations into the immunogenicity of TAAs and TAA-based vaccine strategies in tumors with low levels of T-cell exhaustion.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1589-1602"},"PeriodicalIF":8.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970677","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}

{"title":"Alternate MHC I antigen presentation pathways allow CD8+ T-cell recognition and killing of cancer cells in the absence of ß2M or TAP.","authors":"Freidrich Cruz, Laura A A Orellano, Amanda Chan, Kenneth L Rock","doi":"10.1158/2326-6066.CIR-24-0320","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-24-0320","url":null,"abstract":"<p><p>Major histocpmpatibilty complex class I (MHC I) antigen presentation allows CD8+ T cells to detect and eliminate cancerous or virally infected cells. The MHC I pathway is not essential for cell growth and viability and consequently cancers and viruses can evade control by CD8+ T cells by inactivating antigen presentation. In cancers, two common ways for this evasion are the loss of either the MHC I light chain (ß2M) or the cytosol-to-endoplasmic reticulum (ER) peptide transporter (TAP). ß2M-null cells are generally thought to lack the MHC I pathway because the MHC I heavy chain by itself lacks the proper conformation for peptide display. TAP-null cells are thought to have severely defective MHC I antigen presentation because they are incapable of supplying peptides from the cytosol to MHC I molecules in the ER. However, we have found that highly reactive memory CD8+ T cells could still recognize cells that completely lacked ß2M or TAP. This was at least in part because in TAPnull cells, the Sec62 component of the Sec61 translocon supported the transfer of cytosolic peptides into the ER. In ß2M-negative cells, free MHC I heavy chains were able to bind peptides and assume a conformation that was sufficiently recognized by CD8+ T cells. This process required ER chaperones and the peptide-loading complex. We found that these mechanisms supported antigen presentation at a level that was sufficient for memory CD8+ T cells to kill melanoma cells both in vitro and in tumor-bearing mice. The implications for tumor immunotherapy are discussed.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562642","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":"BTN2A1: A Novel Target to Boost Tumor Killing Capacity of Human γδ T Cells.","authors":"Dieter Kabelitz","doi":"10.1158/2326-6066.CIR-24-0925","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-24-0925","url":null,"abstract":"<p><p>γδ T cells have recently raised great interest as effector cells in cancer immunotherapy because of their HLA-independent mode of action and their broad tumor reactivity. To translate the application of γδ T cells into clinically effective immunotherapies, specific tumor targeting and/or boosting of γδ T-cell activation in vivo seem to be a critical step. In this issue, Le Floch and colleagues report a new strategy for enabling γδ T cells to be specifically activated to kill acute lymphoblastic leukemia cells and solid tumor cells using agonistic BTN2A1 antibodies. See related article by Le Floch et al., p. XX .</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"OF1"},"PeriodicalIF":8.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543906","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":"Gefitinib Reverses PD-L1-Mediated Immunosuppression Induced by long-term Glutamine blockade in Bladder Cancer.","authors":"Guofeng Ma, Huiqing Jia, Zhiqiang Li, Xiangyan Zhang, Liping Wang, Zhilei Zhang, Yujing Xiao, Zhijuan Liang, Dan Li, Yuanbin Chen, Xintao Tian, Yonghua Wang, Ye Liang, Haitao Niu","doi":"10.1158/2326-6066.CIR-24-0039","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-24-0039","url":null,"abstract":"<p><p>Glutamine is a major energy source for tumor cells and blocking glutamine metabolism is being investigated as a promising strategy for cancer therapy. However, the antitumor effect of glutamine blockade in bladder cancer remains unclear, necessitating further investigation. Here, we demonstrated that glutamine metabolism was involved in the malignant progression of bladder cancer. Treatment with the glutamine antagonist 6-Diazo-5-oxo-L-norleucine (DON) inhibited the growth of bladder cancer cells in vitro in several ways. In addition, we observed inhibition of tumor growth in bladder cancer-bearing mice using JHU083, a prodrug that was designed to prevent DON-induced toxicity. However, the antitumor immune effect of T cells changed from activation to inhibition as the administrated time extended. We found that both in vitro treatment with DON and in vivo prolonged administration of JHU083 led to the upregulation of PD-L1 in bladder cancer cells. Mechanistically, glutamine blockade up-regulated PD-L1 expression in bladder cancer cells by accumulating ROS, subsequently activating the EGFR/ERK/C-Jun signaling pathway. Combination treatment of JHU083 and gefitinib reversed the up-regulation of PD-L1 in bladder cancer cells induced by prolonged glutamine blockade, resulting in the alleviation of T-cell immunosuppression and a significant improvement in therapeutic outcome. These preclinical findings show promise for glutamine metabolism targeting as a viable therapeutic strategy for bladder cancer, with the potential for further enhancement through combined treatment with gefitinib.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521079","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":"CD27-Armored BCMA CAR T Cell Therapy (CBG-002) for Relapsed and Refractory Multiple Myeloma: A Phase I Clinical Trial.","authors":"Yang Xu, Xuzhao Zhang, Dijia Xin, Jiawei Zhang, Luyao Wang, Yili Fan, Boxiao Chen, Wen Lei, Xi Qiu, Huawei Jiang, Xibin Xiao, Liansheng Huang, Jiandong Yu, Xin Yang, Wenjun Yang, Jiangao Zhu, Wenbin Qian","doi":"10.1158/2326-6066.CIR-24-0051","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-24-0051","url":null,"abstract":"<p><p>B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy has been approved for the treatment of relapsed and refractory multiple myeloma (RRMM); however, whether patients have long-term response has yet to be established. We investigated the feasibility of CBG-002, an CD27-armored BCMA CAR T therapy, to improve clinical efficacy in patients with RRMM. We present preclinical data showing the activity of CBG-002 against myeloma and results from a phase I clinical trial (NCT04706936) evaluating its safety and efficacy in patients with RRMM. The primary endpoint was safety, as assessed by grade 3 or 4 adverse events(AEs). Key secondary endpoints were overall response rate (ORR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). A total of 11 patients were enrolled and received CBG-002 therapy. Nine patients developed grade 1 or 2 cytokine release syndrome (CRS), while no patients experienced grade 3 or higher CRS or immune effector cell-associated neurotoxicity syndrome. Other grade 3 or higher AEs included neutropenia (72.7%), thrombocytopenia (45.5%) and anemia (36.4%). At a median follow-up of 16.7 months, the ORR was 81.8%, including a stringent complete response/complete response rate of 45.5%, very good partial response rate of 18.2%, and partial response rate of 18.2%, with a median DOR of 8.9 (range 1.8-21.9) months. The median OS was not reached, and the median PFS was 8.5 (2.7-22.9) months. In this phase I study, CBG-002, a CD27-armored BCMA CAR T therapy, demonstrated safety and clinical efficacy in patients with RRMM.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458699","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":"Preclinical development of T cells engineered to express a T cell antigen coupler (TAC) targeting Claudin 18.2-positive solid tumors.","authors":"Stacey X Xu, Ling Wang, Philbert Ip, Ritu R Randhawa, Tania Benatar, Suzanna L Prosser, Prabha Lal, Alima Naim Khan, Thanyashanthi Nitya-Nootan, Gargi Thakor, Heather MacGregor, Danielle Hayes, Andrea Vucicevic, Princy Mathew, Sadhak Sengupta, Christopher W Helsen, Andreas G Bader","doi":"10.1158/2326-6066.CIR-24-0138","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-24-0138","url":null,"abstract":"<p><p>The T cell antigen coupler (TAC) is a chimeric receptor that facilitates tumor antigen-specific activation of T cells by co-opting the endogenous T cell receptor complex in the absence of tonic signaling. Previous data demonstrates that TAC affords T cells with the ability to induce durable and safe anti-tumor responses in preclinical models of hematological and solid tumors. Here, we describe the preclinical pharmacology and safety of an autologous Claudin 18.2 (CLDN18.2)-directed TAC T cell therapy, TAC01-CLDN18.2, in preparation for a Phase I/II clinical study in subjects with CLDN18.2-positive solid tumors. Following a screen of putative TAC constructs, the specificity, activity, and cytotoxicity of TAC T cells expressing the final CLDN18.2-TAC receptor were evaluated in vitro and in vivo using gastric, gastroesophageal, and pancreatic tumor models as well as human cells derived from normal tissues. CLDN18.2-specific activity and cytotoxicity of CLDN18.2-TAC T cells were observed in coculture with various 2D tumor cultures naturally expressing CLDN18.2 as well as tumor spheroids. These effects occurred in models with low antigen levels and was positively associated with increasing CLDN18.2 expression. CLDN18.2-TAC T cells effectively eradicated established tumor xenografts in mice in the absence of observed off-target or on-target/off-tumor effects, elicited durable efficacy in recursive killing and tumor rechallenge experiments, and remained unreactive in coculture with human cells representing vital organs. Thus, the data demonstrate that CLDN18.2-TAC T cells can induce a specific and long-lasting anti-tumor response in various CLDN18.2-positive solid tumor models without notable TAC-dependent toxicities, supporting the clinical development of TAC01-CLDN18.2.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458700","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}