Review
Oncology
Erden Atilla, Karim Benabdellah
Summary: Despite limited progress in adoptive cellular therapies for relapsed/refractory AML compared to B cell malignancies, CAR T cell Phase I trials targeting single antigens have been established worldwide with around 100 patients recruited. The high heterogeneity in AML patients at genetic and molecular levels poses unique therapeutic challenges. This review discusses the need for new perspectives and presents promising novel strategies, including advanced CAR T, TCR-T, and CAR NK therapies, tailored microenvironment and neoantigen targeting, as well as allogeneic approaches.
Article
Oncology
Alessia Volpe, Veronica L. Nagle, Jason S. Lewis, Vladimir Ponomarev
Summary: CAR-T cell therapy has made unprecedented advances in treating hematologic cancers, but there is a lack of readily translatable imaging approaches to visualize the dynamics of CAR-T cells in vivo. Noninvasive PET imaging is considered the ideal tool for monitoring CAR-T cells.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Laura Hidalgo, Beatriz Somovilla-Crespo, Patricia Garcia-Rodriguez, Alvaro Morales-Molina, Miguel Angel Rodriguez-Milla, Javier Garcia-Castro
Summary: We report a switchable CAR T cell strategy using anti-FITC CAR T cells and a switch molecule conjugated with FITC for targeting osteosarcoma (OS) tumors. The presence of the anti-B7-H3-FITC mAb switch is crucial for the effector functions of anti-FITC CAR T cells against OS, including tumor cell killing activity and cytokine production. In vivo, the switchable CAR T cells exert an antitumor effect in an OS NSG mouse model only in the presence of the switch molecule.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Chemistry, Multidisciplinary
Qiang Zeng, Zhigang Liu, Ting Niu, Chuan He, Ying Qu, Zhiyong Qian
Summary: Cellular immunotherapy involves reinjecting in vitro modified immunocytes into patients to target and kill tumor cells. Chimeric antigen receptor T cell (CAR-T) therapy, as a successful representative of tumor cellular immunotherapy, has shown promising results in treating relapsed/refractory hematological tumors. However, challenges such as the limited effectiveness in solid tumors, cytokine release syndrome (CRS) or CAR-T-related encephalopathy syndrome (CRES), off-target effects, and high costs remain. Nanotechnology offers advantages in CAR construction, T cell transfection, expansion, delivery, antitumor effects, and reducing toxicities. This review summarizes the nanotechnologies used in CAR-T immunotherapy and discusses the future directions and challenges of combining nanotechnologies with CAR-T immunotherapy.
CHINESE CHEMICAL LETTERS
(2023)
Article
Oncology
Paresh Vishwasrao, Gongbo Li, Justin C. Boucher, D. Lynne Smith, Susanta K. Hui
Summary: CAR-T cell therapy is a promising cancer treatment method, but it also brings about some immune-related toxicities. Impressive results have been achieved in treating B cell hematological malignancies, but further research is needed for other hematological malignancies. This article summarizes the findings from preclinical and human studies of CAR-T cell therapy and discusses new treatment targets.
Article
Oncology
Jitendra Kumar, Ritesh Kumar, Amir Kumar Singh, Elviche L. Tsakem, Mahesh Kathania, Matthew J. Riese, Arianne L. Theiss, Marco L. Davila, K. Venuprasad
Summary: The study identified Cbl-b as a potential target for overcoming exhausted CAR T-cell function in solid tumors. Inhibition of Cbl-b restored effector function of exhausted T cells. Depletion of Cbl-b enhanced CAR T-cell efficacy in reducing tumor growth, decreasing exhausted T cells, and increasing effector cytokine expression.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Karen Kai-Lin Fang, Jongbok Lee, Ismat Khatri, Yoosu Na, Li Zhang
Summary: The use of allogeneic CAR4-DNTs as adoptive cell therapy for T-cell malignancies is effective. CAR4-DNTs can effectively target T-ALL and PTCL and have superior cytotoxicity compared to empty-vector transduced DNTs.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Immunology
Anqi Ren, Xiqin Tong, Na Xu, Tongcun Zhang, Fuling Zhou, Haichuan Zhu
Summary: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with high relapse rates and poor prognosis. Current guidelines do not recommend specific treatments, and allogeneic stem cell transplant is the only curative therapy with potential risks. Recent trials have shown success in treating hematologic malignancies with immunotherapies such as monoclonal antibodies, checkpoint inhibitors, and CAR T therapies. However, developing CAR T immunotherapy for T-ALL is challenging due to potential risks of fratricide, T-cell aplasia, immunosuppression, and product contamination.
Article
Oncology
Behnia Akbari, Zahra Hosseini, Pardis Shahabinejad, Saba Ghassemi, Hamid Reza Mirzaei, Roddy S. O'Connor
Summary: This article focuses on the functional impairments of CAR T cells in tumor microenvironments, where tumor cell metabolism and nutrient competition affect the differentiation and function of CAR T cells' progeny. Metabolic intermediates shape the immune response by influencing epigenetic programs.
Article
Oncology
Xin Jin, Danni Xie, Rui Sun, Wenyi Lu, Xia Xiao, Yibing Yu, Juanxia Meng, Mingfeng Zhao
Summary: In this study, dual-targeted CAR-T (123NL CAR-T) cells were developed to eradicate AML cells and selectively target immunosuppressive cells. The incorporation of a highly compact marker/suicide gene, RQR8, allowed for the elimination of CAR-T cells and cessation of their cytotoxicity. This approach can overcome the limitations of single-target CAR-T therapy in AML.
Article
Chemistry, Medicinal
Jeong Hyeon Cha, Eunsu Kim, Hyeong Ji Lee, Young-Ho Lee, Jeonghyun Lee, Eunha Kim, Chan Hyuk Kim
Summary: Metabolic glycan labeling combined with CAR-T cell therapy can provide novel cancer immunotherapy for solid tumors that lack viable target antigens.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Medicine, Research & Experimental
Meng Zhang, Xin Jin, Rui Sun, Xia Xiong, Jiaxi Wang, Danni Xie, MingFeng Zhao
Summary: CAR-T cell therapy has shown significant efficacy in treating hematological malignancies, but faces challenges in solid tumor therapy. Researchers have been focusing on improving the metabolic adaptability and antitumor activity of CAR-T cells, leading to some breakthroughs in recent years.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Rodrigo C. C. De Marco, Hector J. J. Monzo, Paivi M. Ojala
Summary: With the continuous advancements in immunotherapy and precision medicine, adoptive cell therapy (ACT) has emerged as a new treatment approach in oncology. Chimeric antigen receptor (CAR) T cells, genetically modified lymphocytes, have shown promising results in targeting and killing cancer cells. Commercialization of CAR T cell therapy has paved the way for future bright developments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, General & Internal
Diana Gumber, Leo D. Wang
Summary: Chimeric antigen receptor (CAR) T cell therapy has shown impressive antitumor activity in the treatment of hematological malignancies, but CAR T cell exhaustion remains a major limitation. This review discusses the underlying mechanisms of exhaustion and emerging strategies to prevent or reverse exhaustion through modifications of the CAR receptor or CAR independent pathways. These strategies hold potential for improving the clinical outcomes of CAR T cell therapy.
Review
Biochemistry & Molecular Biology
Ashanti Concepcion Uscanga-Palomeque, Ana Karina Chavez-Escamilla, Cynthia Aracely Alvizo-Baez, Santiago Saavedra-Alonso, Luis Daniel Terrazas-Armendariz, Reyes S. Tamez-Guerra, Cristina Rodriguez-Padilla, Juan Manuel Alcocer-Gonzalez
Summary: This paper reviews the latest developments in CAR-T cells in cancer treatment, including the structure and manufacturing methods of different generations and variants. The challenges and limitations of CAR-T technology in treating hematological and solid cancer are discussed, as well as the use of CAR technology in other immune cells. The paper concludes that CAR-T cells have the potential to treat not only cancer but also other chronic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
