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39844819 | 0 | Advancements and Future Directions of Dual-Target Chimeric Antigen Receptor T-Cell Therapy in Preclinical and Clinical Studies. | In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has made groundbreaking progress in the treatment of various cancer types, particularly hematological malignancies. In the meantime, various preclinical and clinical studies have extensively explored dual-target CAR-T therapies which can be designed to recognize two antigens simultaneously based on the immunophenotype of tumor cells. Compared with single-target CAR-T approach, dual-target CAR-T therapies demonstrate varying degrees of superior antitumor CAR effects, prevent antigen escape and relapse, reduce on-target off-tumor effects, and ensure durable responses in different types of cancer. These advantages highlight the potential future prospects in this field, showing varying degrees of advancement in preclinical and clinical studies. Herein, we aimed to review different dual-target CAR-T studies conducted on a wide range of tumor models, summarizing the selection of target combinations, the efficacy and safety demonstrated in preclinical and clinical settings, the existing limitations, and the potential future directions of this promising therapeutic strategy. | [
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"advancement",
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"this promising therapeutic strategy",
"two antigens",
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] | [
"cancer immunotherapy",
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"hematological malignancies",
"solid tumors"
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10.21037/tcr-22-174 | [
"Zhang",
"Liu"
] | [
"School of Medicine, University of Tsinghua, Beijing, China.\nDivision of Hematology-Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.",
"Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."
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39844295 | 1 | Application of adoptive cell therapy in malignant melanoma. | Cutaneous melanoma is one of the most aggressive skin cancers originating from skin pigment cells. Patients with advanced melanoma suffer a poor prognosis and generally cannot benefit well from surgical resection and chemo/target therapy due to metastasis and drug resistance. Thus, adoptive cell therapy (ACT), employing immune cells with specific tumor-recognizing receptors, has emerged as a promising therapeutic approach to display on-tumor toxicity. This review discusses the application, efficacy, limitations, as well as future prospects of four commonly utilized approaches -including tumor-infiltrating lymphocytes, chimeric antigen receptor (CAR) T cell, engineered T-cell receptor T cells, and chimeric antigen receptor NK cells- in the context of malignant melanoma. | [
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10.3389/fimmu.2023.1212546 | [
"Hu",
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"Wang",
"Shen",
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"Department of Plastic and Reconstructive Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China.",
"Department of Plastic and Reconstructive Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China.",
"Department of Plastic and Reconstructive Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China.",
"Department of Plastic and Reconstructive Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China.",
"Department of Plastic and Reconstructive Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China.",
"Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.",
"Department of Plastic and Reconstructive Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China. [email protected].\nCancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. [email protected].",
"Department of Plastic and Reconstructive Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China. [email protected].\nCancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. [email protected]."
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39844281 | 2 | Knockout IL4I1 affects macrophages to improve poor efficacy of CD19 CAR-T combined with PD-1 inhibitor in relapsed/refractory diffuse large B-cell lymphoma. | Chimeric antigen receptor (CAR) T-cell therapy plays a critical role in the treatment of B-cell hematologic malignancies. The combination of PD-1 inhibitors and CAR-T has shown encouraging results in treating patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, there are still cases where treatment is ineffective. This study aimed to investigate the role of IL4I1 in the poor efficacy of CD19 CAR-T combined with PD-1 inhibitors in R/R DLBCL and to explore potential mechanisms. Transcriptomic and metabolomic correlation analyses were performed on tumor tissue from DLBCL patients. We employed an in vitro co-culture system consisting of Pfeiffer cells, CD19 CAR-T and macrophages to investigate the underlying mechanisms. It was found that IL4I1 levels were significantly increased in the tumor tissues of R/R DLBCL patients compared to responders. Correlation analysis revealed a positive association between IL4I1 and tryptophan (Trp)-kynurenic acid (Kyn) related metabolites. In the in vitro co-culture model, the presence of IL4I1 inhibited the cytotoxicity of CAR-T cells. Depletion of IL4I1 disrupted the IDO-AHR-Kyn signaling pathway, thereby enhancing the effectiveness of PD-1 inhibitors in combination with CD19 CAR-T for DLBCL treatment. CAR-T-mediated cytotoxicity was significantly inhibited when IL4I1 was present in the in vitro co-culture model. These findings suggest that IL4I1 may be a contributing factor to poor prognosis in R/R DLBCL patients. IL4I1 expression enhances immunosuppression via the IDO-AHR-Kyn pathway, inhibiting the effectiveness of PD-1 inhibitors combined with CD19 CAR-T. Therefore, suppression of IL4I1 may represent a potential target for combination therapy in DLBCL. | [
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10.1158/1078-0432.CCR-19-3874 | [
"Zhang",
"Zhang",
"Xiao",
"Liu",
"Zhao"
] | [
"Department of Hematology, Tianjin First Central Hospital, Tianjin, China.",
"Department of Hematology, First Center Clinic College of Tianjin Medical University, Tianjin, China.",
"Boyalife wsn ltd, Shen Zhen, China.",
"Boyalife wsn ltd, Shen Zhen, China. [email protected].",
"Department of Hematology, Tianjin First Central Hospital, Tianjin, China. [email protected].\nDepartment of Hematology, First Center Clinic College of Tianjin Medical University, Tianjin, China. [email protected]."
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39843688 | 3 | Evolving Immunotherapy Strategies in Gastrointestinal Neuroendocrine Neoplasms. | Treatment for neuroendocrine neoplasms (NENs) is tailored to the tumor's site of origin, grade, and differentiation. NENs are categorized into two main types: well-differentiated neuroendocrine tumors (NETs), which tend to grow more slowly and are less aggressive, and poorly differentiated neuroendocrine carcinomas (NECs), which are highly aggressive and harder to treat. Treatment options for NETs range from somatostatin analogues and mTOR inhibitors to peptide receptor radionuclide therapy (PRRT) with Lutetium-177 dotatate. In cases where the disease progresses more rapidly, cytotoxic chemotherapy may also be considered. In contrast, chemotherapy plays a central role in treating NECs, often following protocols similar to those used for small cell lung cancer. Exciting progress is being made in the development of new therapies for NENs. Inspired by the success of immunotherapy in other cancers, clinical trials have begun to explore its potential in NENs. Early findings suggest that immune checkpoint inhibitors (ICIs) may offer benefits, especially in patients with higher-grade NETs and NECs. However, because NENs have an immunologically "cold" tumor microenvironment-meaning they are less likely to trigger an immune response-new strategies are needed to boost ICI efficacy. To overcome this challenge, researchers are exploring innovative approaches, such as combining dual ICIs or pairing ICIs with other therapeutic agents to make the tumors more responsive to immune attack. Moreover, there is growing enthusiasm for cutting-edge therapies designed to enhance the immune system's ability to recognize and destroy cancer cells. These include bispecific T cell engagers, chimeric antigen receptor T cells, tumor-infiltrating lymphocytes, oncolytic viruses, and cancer vaccines. While their effectiveness in NENs is still being studied, these approaches hold considerable promise, offering new hope for patients with this challenging and complex cancer type. | [
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39841845 | 4 | Microenvironment actuated CAR T cells improve solid tumor efficacy without toxicity. | A major limiting factor in the success of chimeric antigen receptor (CAR) T cell therapy for the treatment of solid tumors is targeting tumor antigens also found on normal tissues. CAR T cells against GD2 induced rapid, fatal neurotoxicity because of CAR recognition of GD2 | [
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"solid tumors",
"CAR recognition",
"GD2",
"normal tissues",
"CAR",
"rapid, fatal neurotoxicity",
"A major limiting factor",
"the success",
"the treatment"
] | [] | 0 | 10.1126/sciadv.ads3403 | [
"Vogt",
"Silberman",
"Lin",
"Han",
"Laflin",
"Gellineau",
"Heller",
"Scheinberg"
] | [
"Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.\nGraduate School of Medical Sciences, Weill Cornell Medicine, New York, NY 10065, USA.\nTri-Institutional PhD Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.",
"Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.\nGraduate School of Medical Sciences, Weill Cornell Medicine, New York, NY 10065, USA.\nPharmacology Program, Weill Cornell Medicine, New York, NY 10065, USA.",
"Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.\nGraduate School of Medical Sciences, Weill Cornell Medicine, New York, NY 10065, USA.\nBCMB Program, Weill Cornell Medicine, New York, NY 10065, USA.",
"Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.",
"Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.",
"Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.",
"Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.\nGraduate School of Medical Sciences, Weill Cornell Medicine, New York, NY 10065, USA.\nTri-Institutional PhD Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.\nPharmacology Program, Weill Cornell Medicine, New York, NY 10065, USA.",
"Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.\nGraduate School of Medical Sciences, Weill Cornell Medicine, New York, NY 10065, USA.\nTri-Institutional PhD Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.\nPharmacology Program, Weill Cornell Medicine, New York, NY 10065, USA."
] | [
"39841845"
] | [] | 9.616429 | 6.79694 |
39841806 | 5 | Triple knockdown of | "Chimeric antigen receptor (CAR)-T cell therapies have revolutionized the landscape of cancer treatm(...TRUNCATED) | [0.013676300644874573,0.025339338928461075,0.047948043793439865,0.07261629402637482,-0.0426719076931(...TRUNCATED) | 2025-01-22 | 1 | 39841806 | ["CAR)-T cell therapies","solid tumors","tumor","Chimeric antigen receptor","improved CAR-T cell the(...TRUNCATED) | [] | 0 | 10.1126/scitranslmed.adl6432 | ["Wang","Wu","Cui","Bian","Zheng","Zhu","Geng","Sun","Pan","Shi","Yi","Song","Li","Shen","Li","Shen"(...TRUNCATED) | ["Department of Interventional Oncology, Renji Hospital, Shanghai Jiao Tong University School of Med(...TRUNCATED) | [
"39841806"
] | [] | 8.998252 | 5.280612 |
39840882 | 6 | [Patient with diffuse large B-cell lymphoma: a good example of network in care.]. | "Chimeric Antigen Receptor T cell (CAR-T) therapy has revolutionized prognosis of patients with diff(...TRUNCATED) | [0.018854942172765732,0.02260638028383255,0.052886709570884705,0.06867451965808868,-0.02425603568553(...TRUNCATED) | 2025-01-22 | 1 | 39840882 | ["marginal zone lymphoma","holding therapy","early referral","complete remission","diffuse large B-c(...TRUNCATED) | [] | 0 | 10.1701/4416.44128 | [
"Tisi"
] | [
"UO Ematologia, Ospedale San Bortolo, Vicenza."
] | [
"39840882"
] | [] | 6.266233 | 5.473475 |
39839908 | 7 | "A bioluminescent reporter bioassay for in-process assessment of chimeric antigen receptor lentivira(...TRUNCATED) | "Chimeric antigen receptor (CAR)-T-cell therapy is a breakthrough in the field of cancer immunothera(...TRUNCATED) | [-0.0014690025709569454,-0.01320493035018444,-0.009483763948082924,0.024350037798285484,-0.019641874(...TRUNCATED) | 2025-01-22 | 22 | 39839908 | ["CAR LV","LV potency","LV MOA","LV quantification","T cells","activated T cells","patient T cells",(...TRUNCATED) | [
"CAR-T",
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] | 0 | "10.1093/abt/tbae032\n10.1016/j.ebiom.2020.102931\n10.1038/nbt0102-70\n10.4049/jimmunol.172.1.104\n1(...TRUNCATED) | [
"Gilden",
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] | ["Research and Development, Promega Corp., Madison, WI 53711, United States.","Research and Developm(...TRUNCATED) | ["39839908","32739874","11753365","14688315","20683006","37215709","36253252","16836756","38282894",(...TRUNCATED) | [] | 8.165737 | 4.711771 |
39837618 | 8 | Art of TIL immunotherapy: SITC's perspective on demystifying a complex treatment. | "In a first for solid cancers, cellular immunotherapy has entered standard of care in the treatment (...TRUNCATED) | [-0.029780112206935883,0.007054430432617664,0.02348320372402668,0.03451462835073471,-0.0084570311009(...TRUNCATED) | 2025-01-22 | 61 | 39837618 | ["TIL immunotherapy","TIL manufacturing","TIL","clinical practice guidelines","underlying clinical r(...TRUNCATED) | ["Adoptive cell therapy - ACT","Cytokine","Immunotherapy","Surgery","Tumor infiltrating lymphocyte -(...TRUNCATED) | 0 | "10.1136/jitc-2024-010207\n10.1126/science.aad1253\n10.1172/JCI82416\n10.1016/j.ccell.2023.11.005\n1(...TRUNCATED) | ["Turcotte","Donia","Gastman","Besser","Brown","Coukos","Creelan","Mullinax","Sondak","Yang","Rohaan(...TRUNCATED) | ["Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada.","Department of Oncol(...TRUNCATED) | ["39837618","26516200","26389673","38039963","37820582","3489291","3264384","12242449","34413159","3(...TRUNCATED) | [] | 10.194453 | 4.454338 |
39836430 | 9 | "Population Pharmacokinetics of Orvacabtagene Autoleucel, an Autologous BCMA-Directed Chimeric Antig(...TRUNCATED) | "Orvacabtagene autoleucel (orva-cel; JCARH125), a CAR T-cell therapy targeting B-cell maturation ant(...TRUNCATED) | [0.03012278489768505,0.003520004218444228,0.03740132227540016,0.01596098765730858,-0.070713579654693(...TRUNCATED) | 2025-01-21 | 1 | 39836430 | ["CAR+ T cells","T cell biology","Traditional piecewise models","plasma cells","traditional models",(...TRUNCATED) | [] | 0 | 10.1158/1078-0432.CCR-24-2753 | [
"Hu",
"Li",
"Piasecki",
"Hosseyni",
"Yan",
"Liu",
"Ogasawara",
"Zhou",
"Cheng"
] | ["Bristol-Myers Squibb (United States), Princeton, New Jersey, United States.","Bristol-Myers Squibb(...TRUNCATED) | [
"39836430"
] | [] | 5.44703 | 5.483919 |
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