Molecular Therapy: Oncology最新文献_第3页

Targeting the membrane-proximal C2-set domain of CD33 for improved CAR T cell therapy 靶向 CD33 的膜近端 C2-set 结构域，改进 CAR T 细胞疗法

Molecular Therapy: Oncology Pub Date : 2024-07-31 DOI: 10.1016/j.omton.2024.200854

Salvatore Fiorenza, Sheryl Y.T. Lim, George S. Laszlo, Erik L. Kimble, Tinh-Doan Phi, Margaret C. Lunn-Halbert, Delaney R. Kirchmeier, Jenny Huo, Hans-Peter Kiem, Cameron J. Turtle, Roland B. Walter

{"title":"Targeting the membrane-proximal C2-set domain of CD33 for improved CAR T cell therapy","authors":"Salvatore Fiorenza, Sheryl Y.T. Lim, George S. Laszlo, Erik L. Kimble, Tinh-Doan Phi, Margaret C. Lunn-Halbert, Delaney R. Kirchmeier, Jenny Huo, Hans-Peter Kiem, Cameron J. Turtle, Roland B. Walter","doi":"10.1016/j.omton.2024.200854","DOIUrl":"https://doi.org/10.1016/j.omton.2024.200854","url":null,"abstract":"Current CD33-targeted immunotherapies typically recognize the membrane-distal V-set domain of CD33. Here, we show that decreasing the distance between T cell and leukemia cell membrane increases the efficacy of CD33 chimeric antigen receptor (CAR) T cells. We therefore generated and optimized second-generation CAR constructs containing single-chain variable fragments from antibodies raised against the membrane-proximal C2-set domain, which bind CD33 regardless of whether the V-set domain is present (CD33 antibodies). CD33 CAR T cells resulted in efficient tumor clearance and improved survival of immunodeficient mice bearing human AML cell xenografts and, in an AML model with limited CD33 expression, forced escape of CD33 leukemia. Compared to CD33 CAR T cells, CD33 CAR T cells showed greater and efficacy against several human AML cell lines with differing levels of CD33 without increased expression of exhaustion markers. CD33 moieties were detected at a higher frequency on human leukemic stem cells, and CD33 CAR T cells had greater efficacy against primary human AML cells. Together, our studies demonstrate improved efficacy with CAR T cells binding CD33 close to the cell membrane, providing the rationale to investigate CD33 CAR T cells further toward possible clinical application.","PeriodicalId":519910,"journal":{"name":"Molecular Therapy: Oncology","volume":"239 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141930570","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}

引用次数: 0

Advances in cell-based delivery of oncolytic viruses as therapy for lung cancer 以细胞为基础输送溶瘤病毒治疗肺癌的进展

Molecular Therapy: Oncology Pub Date : 2024-07-23 DOI: 10.1016/j.omton.2024.200848

Giti Esmail Nia, Elahe Nikpayam, Molood Farrokhi, Azam Bolhassani, Ralph Meuwissen

引用次数: 0

T cell receptor-directed antibody-drug conjugates for the treatment of T cell-derived cancers 用于治疗 T 细胞衍生癌症的 T 细胞受体导向抗体-药物共轭物

Molecular Therapy: Oncology Pub Date : 2024-07-19 DOI: 10.1016/j.omton.2024.200850

Katrin Schoenfeld, Jan Habermann, Philipp Wendel, Julia Harwardt, Evelyn Ullrich, Harald Kolmar

{"title":"T cell receptor-directed antibody-drug conjugates for the treatment of T cell-derived cancers","authors":"Katrin Schoenfeld, Jan Habermann, Philipp Wendel, Julia Harwardt, Evelyn Ullrich, Harald Kolmar","doi":"10.1016/j.omton.2024.200850","DOIUrl":"https://doi.org/10.1016/j.omton.2024.200850","url":null,"abstract":"T cell-derived cancers are hallmarked by heterogeneity, aggressiveness, and poor clinical outcomes. Available targeted therapies are severely limited due to a lack of target antigens that allow discrimination of malignant from healthy T cells. Here, we report a novel approach for the treatment of T cell diseases based on targeting the clonally rearranged T cell receptor displayed by the cancerous T cell population. As a proof of concept, we identified an antibody with unique specificity toward a distinct T cell receptor (TCR) and developed antibody-drug conjugates, precisely recognizing and eliminating target T cells while preserving overall T cell repertoire integrity and cellular immunity. Our anti-TCR antibody-drug conjugates demonstrated effective receptor-mediated cell internalization, associated with induction of cancer cell death with strong signs of apoptosis. Furthermore, cell proliferation-inhibiting bystander effects observed on target-negative cells may contribute to the molecules’ anti-tumor properties precluding potential tumor escape mechanisms. To our knowledge, this represents the first anti-TCR antibody-drug conjugate designed as custom-tailored immunotherapy for T cell-driven pathologies.","PeriodicalId":519910,"journal":{"name":"Molecular Therapy: Oncology","volume":"68 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141784857","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}

引用次数: 0

p53-armed oncolytic virotherapy induces abscopal effect in osteosarcoma by promoting immunogenic cell death 带有 p53 的溶瘤病毒疗法通过促进免疫性细胞死亡诱导骨肉瘤的脱落效应

Molecular Therapy: Oncology Pub Date : 2024-06-29 DOI: 10.1016/j.omton.2024.200845

Koji Demiya, Hiroshi Tazawa, Hiroya Kondo, Miho Kure, Yusuke Mochizuki, Tadashi Komatsubara, Aki Yoshida, Koji Uotani, Joe Hasei, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

{"title":"p53-armed oncolytic virotherapy induces abscopal effect in osteosarcoma by promoting immunogenic cell death","authors":"Koji Demiya, Hiroshi Tazawa, Hiroya Kondo, Miho Kure, Yusuke Mochizuki, Tadashi Komatsubara, Aki Yoshida, Koji Uotani, Joe Hasei, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara","doi":"10.1016/j.omton.2024.200845","DOIUrl":"https://doi.org/10.1016/j.omton.2024.200845","url":null,"abstract":"Osteosarcoma (OS), the most frequent primary malignant tumor of bone in children and adolescents, is refractory to immune checkpoint inhibitors due to its poor antitumor immune response. Chemotherapy and virotherapy induce immunogenic cell death (ICD) and antitumor immune responses, leading to the abscopal effect in untreated tumors. We previously demonstrated the antitumor activity of the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 in human OS cells. Here, we show the therapeutic potential of chemotherapeutic drugs (doxorubicin, cisplatin) and telomerase-specific oncolytic adenoviruses (OBP-301, p53-armed OBP-702) to induce ICD in human OS cells (U2OS, MNNG/HOS, SaOS-2) and murine OS cells (NHOS). OBP-702 induced more profound ICD via the secretion of adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1) compared with chemotherapy and OBP-301 in human OS cells. Murine NHOS cells were also more sensitive to OBP-702 than OBP-301. Subcutaneous NHOS tumor models demonstrated that intratumoral injection of OBP-702 significantly increased the tumor infiltration of cytotoxic CD8+ T cells and induced the abscopal effect against non-treated tumors compared with OBP-301. Our results suggest that OBP-702 is a promising antitumor reagent to induce ICD with secretion of ATP and HMGB1 and the abscopal effect against OS.","PeriodicalId":519910,"journal":{"name":"Molecular Therapy: Oncology","volume":"151 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141585961","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}

引用次数: 0

The reovirus variant RP116 demonstrates oncolytic efficacy in immunocompetent models and generates reduced neutralizing antibodies to Type 3 Dearing 再病毒变体 RP116 在免疫功能健全的模型中显示出溶瘤功效，并产生了较少的 3 型 Dearing 中和抗体

Molecular Therapy: Oncology Pub Date : 2024-06-29 DOI: 10.1016/j.omton.2024.200846

Ki-Hoon Song, Xiao Xiang, So Hyun Lee, Jong Kyu Woo, Gansukh Enkhtaivan, Carlos Rios Giraldo, You-Rim Lee, Yeo Jin Jeong, Salar Pashangzadeh, Negar Sharifi, An-Dao Yang, Huy-Dung Hoang, Nam-Hyuk Cho, Yeon-Sook Lee, Dong Guk Park, Tommy Alain

{"title":"The reovirus variant RP116 demonstrates oncolytic efficacy in immunocompetent models and generates reduced neutralizing antibodies to Type 3 Dearing","authors":"Ki-Hoon Song, Xiao Xiang, So Hyun Lee, Jong Kyu Woo, Gansukh Enkhtaivan, Carlos Rios Giraldo, You-Rim Lee, Yeo Jin Jeong, Salar Pashangzadeh, Negar Sharifi, An-Dao Yang, Huy-Dung Hoang, Nam-Hyuk Cho, Yeon-Sook Lee, Dong Guk Park, Tommy Alain","doi":"10.1016/j.omton.2024.200846","DOIUrl":"https://doi.org/10.1016/j.omton.2024.200846","url":null,"abstract":"The mammalian reovirus Type 3 Dearing (T3D) is a naturally occurring oncolytic virus. We previously identified a T3D variant isolated from persistently infected cancer cells that has a premature stop codon mutation in the gene, generating a truncated σ1-attachment protein that lacks the globular head. We now report on the molecular characterization of this variant, named RP116, and assess its antitumor potential in human cancer cells and syngeneic mouse models. RP116 replicates efficiently in several cancer cell lines, shows reduced dependency for the JAM-A receptor, significantly decreases tumor growth in syngeneic models when injected either intratumorally or intravenously, and generates long-term cures and immune memory in combination with checkpoint inhibitors. Finally, we demonstrate that RP116 infection in mice leads to reduced production of neutralizing antibodies directed against reovirus T3D, preserving the efficacy of subsequent reovirus treatment. These results establish the value of developing RP116 as an additional oncolytic reovirus platform.","PeriodicalId":519910,"journal":{"name":"Molecular Therapy: Oncology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141585965","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}

引用次数: 0

Targeting CD45 by gene-edited CAR T cells for leukemia eradication and hematopoietic stem cell transplantation preconditioning 通过基因编辑的 CAR T 细胞靶向 CD45，用于白血病根除和造血干细胞移植预处理

Molecular Therapy: Oncology Pub Date : 2024-06-27 DOI: 10.1016/j.omton.2024.200843

Valeria M. Stepanova, Dmitry V. Volkov, Daria S. Osipova, Wenjian Wang, Yingqin Hou, Dmitry E. Pershin, Mariia S. Fadeeva, Ekaterina A. Malakhova, Elena A. Kulakovskaya, Lui Cuicui, Zhao Mingfeng, Hongkai Zhang, Jia Xie, Ding Zhang, Ilgar Z. Mamedov, Alexandr S. Chernov, Georgij B. Telegin, Yuri P. Rubtsov, Alexander G. Gabibov, Peng Wu, Michael A. Maschan, Alexey V. Stepanov

{"title":"Targeting CD45 by gene-edited CAR T cells for leukemia eradication and hematopoietic stem cell transplantation preconditioning","authors":"Valeria M. Stepanova, Dmitry V. Volkov, Daria S. Osipova, Wenjian Wang, Yingqin Hou, Dmitry E. Pershin, Mariia S. Fadeeva, Ekaterina A. Malakhova, Elena A. Kulakovskaya, Lui Cuicui, Zhao Mingfeng, Hongkai Zhang, Jia Xie, Ding Zhang, Ilgar Z. Mamedov, Alexandr S. Chernov, Georgij B. Telegin, Yuri P. Rubtsov, Alexander G. Gabibov, Peng Wu, Michael A. Maschan, Alexey V. Stepanov","doi":"10.1016/j.omton.2024.200843","DOIUrl":"https://doi.org/10.1016/j.omton.2024.200843","url":null,"abstract":"Hematopoietic stem cell transplantation (HSCT) is widely used to treat patients with life-threatening hematologic and immune system disorders. Current nontargeted chemo-/radiotherapy conditioning regimens cause tissue injury and induce an array of immediate and delayed adverse effects, limiting the application of this life-saving treatment. The growing demand to replace canonical conditioning regimens has led to the development of alternative approaches, such as antibody-drug conjugates, naked antibodies, and CAR T cells. Here, we introduce a preconditioning strategy targeting CD45 on hematopoietic cells with CAR45 T cells. To avoid fratricide of CD45 CAR T cells, genomic disruption of the CD45 gene was performed on human CD45 CAR T cells in combination with the signaling kinase inhibitor dasatinib. CD45 CAR45 T cells showed high cytotoxicity and depletion of tumor cells These cells were effective in elimination of human hematopoietic cells engrafted in humanized immunodeficient mice by transfusion with human blood-derived hematopoietic stem cells (HSCs). Similarly, CD45 CAR45 natural killer (NK) cells exhibited potent cytotoxicity toward tumor cell lines and human hematopoietic cells . Thus, we provide the proof of concept for the generation and preclinical efficacy of fratricide-resistant CAR45 T and NK cells directed against CD45-expressing tumors and hematopoietic cells.","PeriodicalId":519910,"journal":{"name":"Molecular Therapy: Oncology","volume":"377 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141585962","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}

引用次数: 0

CD38 regulates chronic lymphocytic leukemia proliferation via CD45 phosphatase activity CD38 通过 CD45 磷酸酶活性调节慢性淋巴细胞白血病的增殖

Molecular Therapy: Oncology Pub Date : 2024-06-24 DOI: 10.1016/j.omton.2024.200841

John F. Imbery, Celina Wiik, Julia Heinzelbecker, Jenny K. Jebsen, Mia K. Dobbing, Nunzio Bottini, Stephanie M. Stanford, Ludvig A. Munthe, Geir E. Tjønnfjord, Anders Tveita, Peter Szodoray, Britt Nakken

{"title":"CD38 regulates chronic lymphocytic leukemia proliferation via CD45 phosphatase activity","authors":"John F. Imbery, Celina Wiik, Julia Heinzelbecker, Jenny K. Jebsen, Mia K. Dobbing, Nunzio Bottini, Stephanie M. Stanford, Ludvig A. Munthe, Geir E. Tjønnfjord, Anders Tveita, Peter Szodoray, Britt Nakken","doi":"10.1016/j.omton.2024.200841","DOIUrl":"https://doi.org/10.1016/j.omton.2024.200841","url":null,"abstract":"Chronic lymphocytic leukemia (CLL) growth is dependent on both B cell receptor (BCR) signaling and signals from microenvironmental T helper (Th) cells. We previously described a mechanism where Th cells enhance BCR signaling and proliferation through CD45 phosphatase activity regulation via galectin-1 and CD43. The CLL negative prognostic indicator CD38 is linked to BCR signaling and proliferation, with its expression induced by Th cells. Here, we explore a link between CD38 and CD45 phosphatase activity regulation using patient-derived material in a Th-CLL cell co-culture model. Results demonstrate CD43 and galectin-1 are co-expressed with CD38, defining proliferative CLL cells with augmented CD45 activity. CD38 enzymatic and receptor inhibition regulated CD43 and galectin-1 expression, CD45 activity populations, and CLL proliferation, while leaving Th cells largely unaffected. Mechanistically, - or (galectin-1)-deficient malignant B cell lines further confirmed CD38-mediated regulation of CD45 activity and BCR signaling through CD43 expression and galectin-1 surface binding, while galectin-1 contributed to CD43/CD45 colocalization. Together, this highlights CD38 as an important regulator of CD45 activity via CD43 and galectin-1, in turn acting as a positive modulator of CLL proliferation. Ultimately, the CD38/CD45 molecular hub could be an important therapeutic target in CLL.","PeriodicalId":519910,"journal":{"name":"Molecular Therapy: Oncology","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141550473","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}

引用次数: 0

Potential of sonobiopsy as a novel diagnosis tool for brain cancer 声波活检作为新型脑癌诊断工具的潜力

Molecular Therapy: Oncology Pub Date : 2024-06-24 DOI: 10.1016/j.omton.2024.200840

Li Yan, Kang Fu, Le Li, Qing Li, Xiaodong Zhou

引用次数: 0

Electrophilic proximity-inducing synthetic adapters enhance universal T cell function by covalently enforcing immune receptor signaling 亲电亲近性诱导合成适配体通过共价强化免疫受体信号转导增强通用 T 细胞功能

Molecular Therapy: Oncology Pub Date : 2024-06-24 DOI: 10.1016/j.omton.2024.200842

Nickolas J. Serniuck, Eden Kapcan, Duane Moogk, Allyson E. Moore, Benjamin P.M. Lake, Galina Denisova, Joanne A. Hammill, Jonathan L. Bramson, Anthony F. Rullo

{"title":"Electrophilic proximity-inducing synthetic adapters enhance universal T cell function by covalently enforcing immune receptor signaling","authors":"Nickolas J. Serniuck, Eden Kapcan, Duane Moogk, Allyson E. Moore, Benjamin P.M. Lake, Galina Denisova, Joanne A. Hammill, Jonathan L. Bramson, Anthony F. Rullo","doi":"10.1016/j.omton.2024.200842","DOIUrl":"https://doi.org/10.1016/j.omton.2024.200842","url":null,"abstract":"Proximity-induction of cell-cell interactions via small molecules represents an emerging field in basic and translational sciences. Covalent anchoring of these small molecules represents a useful chemical strategy to enforce proximity; however, it remains largely unexplored for driving cell-cell interactions. In immunotherapeutic applications, bifunctional small molecules are attractive tools for inducing proximity between immune effector cells like T cells and tumor cells to induce tumoricidal function. We describe a two-component system composed of electrophilic bifunctional small molecules and paired synthetic antigen receptors (SARs) that elicit T cell activation. The molecules, termed covalent immune recruiters (CIRs), were designed to affinity label and covalently engage SARs. We evaluated the utility of CIRs to direct anti-tumor function of human T cells engineered with three biologically distinct classes of SAR. Irrespective of the electrophilic chemistry, tumor-targeting moiety, or SAR design, CIRs outperformed equivalent non-covalent bifunctional adapters, establishing a key role for covalency in maximizing functionality. We determined that covalent linkage enforced early T cell activation events in a manner that was dependent upon each SARs biology and signaling threshold. These results provide a platform to optimize universal SAR-T cell functionality and more broadly reveal new insights into how covalent adapters modulate cell-cell proximity-induction.","PeriodicalId":519910,"journal":{"name":"Molecular Therapy: Oncology","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141550472","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}

引用次数: 0

Co-stimulation of CD28/CD40 signaling molecule potentiates CAR-T cell efficacy and stemness CD28/CD40 信号分子的联合刺激可增强 CAR-T 细胞的功效和干性

Molecular Therapy: Oncology Pub Date : 2024-06-18 DOI: 10.1016/j.omton.2024.200837

Wannakorn Khopanlert, Pongsakorn Choochuen, Kajornkiat Maneechai, Nawaphat Jangphattananont, Socheatraksmey Ung, Shingo Okuno, Peter Steinberger, Judith Leitner, Surasak Sangkhathat, Pongtep Viboonjuntra, Seitaro Terakura, Jakrawadee Julamanee

{"title":"Co-stimulation of CD28/CD40 signaling molecule potentiates CAR-T cell efficacy and stemness","authors":"Wannakorn Khopanlert, Pongsakorn Choochuen, Kajornkiat Maneechai, Nawaphat Jangphattananont, Socheatraksmey Ung, Shingo Okuno, Peter Steinberger, Judith Leitner, Surasak Sangkhathat, Pongtep Viboonjuntra, Seitaro Terakura, Jakrawadee Julamanee","doi":"10.1016/j.omton.2024.200837","DOIUrl":"https://doi.org/10.1016/j.omton.2024.200837","url":null,"abstract":"CD19 chimeric antigen receptor T (CD19CAR-T) cells have achieved promising outcomes in relapsed/refractory B cell malignancies. However, recurrences occur due to the loss of CAR-T cell persistence. We developed dual T/B cell co-stimulatory molecules (CD28 and CD40) in CAR-T cells to enhance intense tumoricidal activity and persistence. CD19.28.40z CAR-T cells promoted pNF-κB and pRelB downstream signaling while diminishing NFAT signaling upon antigen exposure. CD19.28.40z CAR-T cells demonstrated greater proliferation, which translated into effective anti-tumor cytotoxicity in long-term co-culture assay. Repetitive weekly antigen stimulation unveiled continuous CAR-T cell expansion while preserving central memory T cell subset and lower expression of exhaustion phenotypes. The intrinsic genes underlying CD19.28.40z CAR-T cell responses were compared with conventional CARs and demonstrated the up-regulated genes associated with T cell proliferation and memory as well as down-regulated genes related to apoptosis, exhaustion, and glycolysis pathway. Enrichment of genes toward T cell stemness, particularly and , was observed. Effective and continuing anti-tumor cytotoxicity was exhibited in both B cell lymphoblastic leukemia and B cell non-Hodgkin lymphoma xenograft models while demonstrating persistent T cell memory signatures. The functional enhancement of CD37.28.40z CAR-T cell activities against CD37 tumor cells was further validated. The modification of dual T/B cell signaling molecules remarkably maximized the efficacy of CAR-T cell therapy.","PeriodicalId":519910,"journal":{"name":"Molecular Therapy: Oncology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141505338","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}

引用次数: 0