keyword
https://read.qxmd.com/read/38536724/in-silico-methods-for-immunogenicity-risk-assessment-and-human-homology-screening-for-therapeutic-antibodies
#1
JOURNAL ARTICLE
Aimee E Mattei, Andres H Gutierrez, Soorya Seshadri, Jacob Tivin, Matt Ardito, Amy S Rosenberg, William D Martin, Anne S De Groot
In silico immunogenicity risk assessment has been an important step in the development path for many biologic therapeutics, including monoclonal antibodies. Even if the source of a given biologic is 'fully human', T cell epitopes that are contained in the sequences of the biologic may activate the immune system, enabling the development of anti-drug antibodies that can reduce drug efficacy and may contribute to adverse events. Computational tools that identify T cell epitopes from primary amino acid sequences have been used to assess the immunogenic potential of therapeutic candidates for several decades...
2024: MAbs
https://read.qxmd.com/read/38534399/modulating-cholesterol-metabolism-via-acat1-knockdown-enhances-anti-b-cell-lymphoma-activities-of-cd19-specific-chimeric-antigen-receptor-t-cells-by-improving-the-cell-activation-and-proliferation
#2
JOURNAL ARTICLE
Qiong Su, Jie Yao, Muhammad Asad Farooq, Iqra Ajmal, Yixin Duan, Cong He, Xuefei Hu, Wenzheng Jiang
CD19-specific CAR-T immunotherapy has been extensively studied for the treatment of B-cell lymphoma. Recently, cholesterol metabolism has emerged as a modulator of T lymphocyte function and can be exploited in immunotherapy to increase the efficacy of CAR-based systems. Acetyl-CoA acetyltransferase 1 (ACAT1) is the major cholesterol esterification enzyme. ACAT1 inhibitors previously shown to modulate cardiovascular diseases are now being implicated in immunotherapy. In the present study, we achieved knockdown of ACAT1 in T cells via RNA interference technology by inserting ACAT1-shRNA into anti-CD19-CAR-T cells...
March 21, 2024: Cells
https://read.qxmd.com/read/38533510/redefining-the-battle-against-colorectal-cancer-a-comprehensive-review-of-emerging-immunotherapies-and-their-clinical-efficacy
#3
REVIEW
Salima Shebbo, Najat Binothman, Manar Darwaish, Hanan A Niaz, Rwaa H Abdulal, Jamilah Borjac, Anwar M Hashem, Ahmad Bakur Mahmoud
Colorectal cancer (CRC) is the third most common cancer globally and presents a significant challenge owing to its high mortality rate and the limitations of traditional treatment options such as surgery, radiotherapy, and chemotherapy. While these treatments are foundational, they are often poorly effective owing to tumor resistance. Immunotherapy is a groundbreaking alternative that has recently emerged and offers new hope for success by exploiting the body's own immune system. This article aims to provide an extensive review of clinical trials evaluating the efficacy of various immunotherapies, including CRC vaccines, chimeric antigen receptor T-cell therapies, and immune checkpoint inhibitors...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38532629/need-for-standardization-of-cytokine-profiling-in-car-t-cell-therapy
#4
JOURNAL ARTICLE
D Nathan Biery, David P Turicek, Caroline Diorio, Brett A Schroeder, Nirali N Shah
With expansion of CAR T-cell therapy and broader utilization of anti-cytokine directed therapeutics for toxicity mitigation, the routine assessment of cytokines may enhance understanding of toxicity profiles, guide therapeutic interventions, and facilitate cross-trial comparisons. As specific cytokine elevations can correlate with and provide insights into CAR T-cell toxicity, mitigation strategies, and response, we explored the reporting of cytokine detection methods and assessed for the correlation of cytokines to CRS and ICANS across clinical trials...
March 25, 2024: Molecular Therapy
https://read.qxmd.com/read/38532515/inflammation-and-acute-cardiotoxicity-in-adult-hematological-patients-treated-with-car-t-cells-results-from-a-pilot-proof-of-concept-study
#5
JOURNAL ARTICLE
Massimiliano Camilli, Marcello Viscovo, Tamara Felici, Luca Maggio, Federico Ballacci, Giacomo Carella, Alice Bonanni, Priscilla Lamendola, Lorenzo Tinti, Antonio Di Renzo, Giulia Coarelli, Eugenio Galli, Giovanna Liuzzo, Francesco Burzotta, Rocco Antonio Montone, Federica SorĂ , Simona Sica, Stefan Hohaus, Gaetano Antonio Lanza, Filippo Crea, Antonella Lombardo, Giorgio Minotti
AIMS: Chimeric Antigen Receptor-T (CAR-T) cell infusion is a rapidly evolving antitumor therapy; however, cardiovascular (CV) complications, likely associated with cytokine release syndrome (CRS) and systemic inflammation, have been reported to occur. The CARdio-Tox study aimed at elucidating incidence and determinants of cardiotoxicity related to CAR-T cell therapy. METHODS: Patients with blood malignancies candidate to CAR-T cells were prospectively evaluated by echocardiography at baseline and 7 and 30 days after infusion...
March 27, 2024: Cardio-Oncology
https://read.qxmd.com/read/38531760/car-t-cell-therapy-a-collaboration-between-authorized-treatment-centers-and-community-oncologists
#6
REVIEW
Michael R Bishop, Gary E Kay
With the approval of the first CAR T-cell products for hematological malignancies in 2017, these autologous cell therapies have changed the treatment paradigm for patients with relapsed or refractory (r/r) non-Hodgkin lymphoma (NHL), who have a poor prognosis and few effective treatment options. Despite the demonstrated clinical benefit in patients with r/r diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma, many patients who are eligible for CAR T-cell therapies do not receive them or are treated with CAR T cells as a later line of therapy at advanced stages of disease...
February 22, 2024: Seminars in Oncology
https://read.qxmd.com/read/38531057/impact-of-race-and-social-determinants-of-health-on-outcomes-in-patients-with-aggressive-b-cell-nhl-treated-with-car-t
#7
JOURNAL ARTICLE
Reem Karmali, Rushad Machhi, Narendranath Epperla, Geoffrey Shouse, Jason T Romancik, Tamara K Moyo, Vaishalee P Kenkre, Thomas A Ollila, Lindsey A Fitzgerald, Brian T Hess, Kevin A David, Ishan Roy, Joanna C Zurko, Sayan Mullick Chowdhury, Kaitlin Annunzio, Robert Ferdman, Rahul S Bhansali, Elyse I Harris, Jieqi Liu, Imran A Nizamuddin, Shuo Ma, Jonathan Moreira, Jane N Winter, Barbara Pro, Deborah M Stephens, Alexey V Danilov, Nirav N Shah, Jonathon B Cohen, Stefan K Barta, Pallawi Torka, Leo I Gordon
Healthcare disparities driven by multiple social, economic, and/or environmental factors lead to inequalities in health outcomes. CAR-T cell immunotherapy is an effective therapy for relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL). However, data are limited on the impact of the convergence of race and social determinants of health on outcomes for patients treated with CAR-T therapy. We examined the impact of interactions between race and insurance type on health care utilization and outcomes in patients treated with CAR-T for aggressive B-NHL...
March 26, 2024: Blood Advances
https://read.qxmd.com/read/38530240/induction-of-immortal-like-and-functional-car-t-cells-by-defined-factors
#8
JOURNAL ARTICLE
Lixia Wang, Gang Jin, Qiuping Zhou, Yanyan Liu, Xiaocui Zhao, Zhuoyang Li, Na Yin, Min Peng
Long-term antitumor efficacy of chimeric antigen receptor (CAR) T cells depends on their functional persistence in vivo. T cells with stem-like properties show better persistence, but factors conferring bona fide stemness to T cells remain to be determined. Here, we demonstrate the induction of CAR T cells into an immortal-like and functional state, termed TIF. The induction of CARTIF cells depends on the repression of two factors, BCOR and ZC3H12A, and requires antigen or CAR tonic signaling. Reprogrammed CARTIF cells possess almost infinite stemness, similar to induced pluripotent stem cells while retaining the functionality of mature T cells, resulting in superior antitumor effects...
May 6, 2024: Journal of Experimental Medicine
https://read.qxmd.com/read/38529506/senolytic-car-t-cells-reverse-aging-associated-defects-in-intestinal-regeneration-and-fitness
#9
Onur Eskiocak, Saria Chowdhury, Vyom Shah, Emmanuella Nnuji-John, Charlie Chung, Jacob A Boyer, Alexander S Harris, Jill Habel, Michel Sadelain, Semir Beyaz, Corina Amor
Intestinal stem cells (ISCs) drive the rapid regeneration of the gut epithelium to maintain organismal homeostasis. Aging, however, significantly reduces intestinal regenerative capacity. While cellular senescence is a key feature of the aging process, little is known about the in vivo effects of senescent cells on intestinal fitness. Here, we identify the accumulation of senescent cells in the aging gut and, by harnessing senolytic CAR T cells to eliminate them, we uncover their detrimental impact on epithelial integrity and overall intestinal homeostasis in natural aging, injury and colitis...
March 22, 2024: bioRxiv
https://read.qxmd.com/read/38528698/ct-demonstration-of-local-cytokine-release-syndrome-involving-the-head-and-neck-following-chimeric-antigen-receptor-t-cell-infusion-therapy
#10
EDITORIAL
Ji Su Ko, Jeong Hyun Lee, Dok Hyun Yoon, Chong Hyun Suh, Sae Rom Chung, Young Jun Choi, Jung Hwan Baek
No abstract text is available yet for this article.
April 2024: Korean Journal of Radiology: Official Journal of the Korean Radiological Society
https://read.qxmd.com/read/38527847/-progress-in-treatment-of-primary-mediastinal-large-b-cell-lymphoma
#11
JOURNAL ARTICLE
L W Chen, J Y Li, L Fan
Primary mediastinal large B-cell lymphoma (PMBCL) is an aggressive B-cell lymphoma originating from the thymus, which has different clinical and biological characteristics from diffuse large B-cell lymphoma, NOS. PMBCL tends to occur in young women, usually presenting as a large anterior mediastinal mass. Most patients are in stage Ⅰ-Ⅱ at the time of presentation. There is no standard prognostic scoring system for PMBCL. Immunochemotherapy is commonly used in the treatment of PMBCL, but the optimal first-line treatment has not been determined, and the status of radiotherapy is controversial...
January 14, 2024: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://read.qxmd.com/read/38527842/-safety-and-efficacy-of-donor-derived-chimeric-antigen-receptor-t-cell-therapy-in-patients-with-relapsed-b-cell-acute-lymphoblastic-leukemia-after-allogeneic-hematopoietic-stem-cell-transplantation
#12
JOURNAL ARTICLE
Y Q Zhuo, S F Tu, X Zhou, J L Yang, L J Zhou, R Huang, Y X Huang, M F Li, B Jin, B Wang, S Q Li, Z T Yuan, L H Zhang, L Liu, S B Wang, Y H Li
Objective: To investigated the safety and efficacy of donor-derived CD19+ or sequential CD19+ CD22+ chimeric antigen receptor T-cell (CAR-T) therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: The data of 22 patients with B-ALL who relapsed after allo-HSCT and who underwent donor-derived CAR-T therapy at the Zhujiang Hospital of Southern Medical University and the 920th Hospital of Joint Logistics Support Force of the People's Liberation Army of China from September 2015 to December 2022 were retrospectively analyzed...
January 14, 2024: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://read.qxmd.com/read/38527836/-efficacy-and-safety-of-chimeric-antigen-receptor-t-cell-therapy-followed-by-allogeneic-hematopoietic-stem-cell-transplantation-in-21-patients-with-ph-like-acute-lymphoblastic-leukemia
#13
JOURNAL ARTICLE
H P Dai, H J Shen, Z Li, W Cui, Q Y Cui, M Y Li, S F Chen, M Q Zhu, D P Wu, X W Tang
Objective: To evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Ph-like acute lymphoblastic leukemia (Ph-ALL) . Methods: Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included, and their clinical data were retrospectively analyzed. Results: Of the 21 patients, 14 were male and 7 were female...
January 14, 2024: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://read.qxmd.com/read/38526025/car-t-cells-for-solid-tumors-developments-to-watch-in-2023
#14
EDITORIAL
Marcel P Trefny, Sebastian Kobold
No abstract text is available yet for this article.
March 25, 2024: Expert Opinion on Biological Therapy
https://read.qxmd.com/read/38525009/emerging-strategies-to-overcome-current-car-t-therapy-dilemmas-exosomes-derived-from-car-t-cells
#15
REVIEW
Dong Hu, Ruyue Yang, Guidan Wang, Hao Li, Xulong Fan, Gaofeng Liang
Adoptive T cells immunotherapy, specifically chimeric antigen receptor T cells (CAR-T), has shown promising therapeutic efficacy in the treatment of hematologic malignancies. As extensive research on CAR-T therapies has been conducted, various challenges have emerged that significantly hampered their clinical application, including tumor recurrence, CAR-T cell exhaustion, and cytokine release syndrome (CRS). To overcome the hurdles of CAR-T therapy in clinical treatment, cell-free emerging therapies based on exosomes derived from CAR-T cells have been developed as an effective and promising alternative approach...
2024: International Journal of Nanomedicine
https://read.qxmd.com/read/38524535/exploring-cellular-immunotherapy-platforms-in-multiple-myeloma
#16
REVIEW
Manh-Cuong Vo, Sung-Hoon Jung, Van-Tan Nguyen, Van-Dinh-Huan Tran, Nodirjon Ruzimurodov, Sang Ki Kim, Xuan-Hung Nguyen, Mihee Kim, Ga-Young Song, Seo-Yeon Ahn, Jae-Sook Ahn, Deok-Hwan Yang, Hyeoung-Joon Kim, Je-Jung Lee
Despite major advances in therapeutic platforms, most patients with multiple myeloma (MM) eventually relapse and succumb to the disease. Among the novel therapeutic options developed over the past decade, genetically engineered T cells have a great deal of potential. Cellular immunotherapies, including chimeric antigen receptor (CAR) T cells, are rapidly becoming an effective therapeutic modality for MM. Marrow-infiltrating lymphocytes (MILs) derived from the bone marrow of patients with MM are a novel source of T cells for adoptive T-cell therapy, which robustly and specifically target myeloma cells...
March 30, 2024: Heliyon
https://read.qxmd.com/read/38524132/a-novel-type-2-innate-lymphoid-cell-based-immunotherapy-for-cancer
#17
JOURNAL ARTICLE
Iryna Saranchova, Clara Wenjing Xia, Stephanie Besoiu, Pablo L Finkel, Samantha L S Ellis, Suresh Kari, Lonna Munro, Cheryl G Pfeifer, Ladan Fazli, Martin E Gleave, Wilfred A Jefferies
Cell-based cancer immunotherapy has achieved significant advancements, providing a source of hope for cancer patients. Notwithstanding the considerable progress in cell-based immunotherapy, the persistently low response rates and the exorbitant costs associated with their implementation still present a formidable challenge in clinical settings. In the landscape of cell-based cancer immunotherapies, an uncharted territory involves Type 2 innate lymphoid cells (ILC2s) and interleukin-33 (IL-33) which promotes ILC2 functionality, recognized for their inherent ability to enhance immune responses...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38521952/enhanced-bacterial-cancer-therapy-delivering-therapeutic-rna-interference-of-c-myc
#18
JOURNAL ARTICLE
Jason S Williams, Adam T Higgins, Katie J Stott, Carly Thomas, Lydia Farrell, Cleo S Bonnet, Severina Peneva, Anna V Derrick, Trevor Hay, Tianqi Wang, Claire Morgan, Sarah Dwyer, Joshua D'Ambrogio, Catherine Hogan, Matthew J Smalley, Lee Parry, Paul Dyson
BACKGROUND: Bacterial cancer therapy was first trialled in patients at the end of the nineteenth century. More recently, tumour-targeting bacteria have been harnessed to deliver plasmid-expressed therapeutic interfering RNA to a range of solid tumours. A major limitation to clinical translation of this is the short-term nature of RNA interference in vivo due to plasmid instability. To overcome this, we sought to develop tumour-targeting attenuated bacteria that stably express shRNA by virtue of integration of an expression cassette within the bacterial chromosome and demonstrate therapeutic efficacy in vitro and in vivo...
March 23, 2024: Cell & Bioscience
https://read.qxmd.com/read/38517338/chimeric-antigen-receptors-cars-in-the-fast-lane-for-rheumatology
#19
JOURNAL ARTICLE
Nathan M Johnson, Fotios Koumpouras
PURPOSE OF REVIEW: Recent advances in hematology-oncology have pioneered cell-mediated elimination of pathologic B-cell populations employing chimeric antigen receptor (CAR) T cells. In this review, we discuss recent adoption of CAR-T treatment for severe refractory autoimmune disease. We highlight unique aspects of the autoimmune model and review current clinical data regarding treatment of rheumatologic disease. RECENT FINDINGS: To date, several CAR-Ts are FDA approved for Multiple Myeloma and B-cell malignancies and have demonstrated extraordinary clinical responses in refractory disease...
May 1, 2024: Current Opinion in Rheumatology
https://read.qxmd.com/read/38517027/high-cd62l-expression-predicts-the-generation-of-chimeric-antigen-receptor-t-cells-with-potent-effector-functions
#20
JOURNAL ARTICLE
Hitomi Kasuya, Haosong Zhang, Yusuke Ito, Toshiaki Yoshikawa, Takahiro Nakashima, Yang Li, Tetsuya Matsukawa, Satoshi Inoue, Yuki Kagoya
Efficient generation of chimeric antigen receptor (CAR) T cells is highly influenced by the quality of apheresed T cells. Healthy donor-derived T cells usually proliferate better than patients-derived T cells and are precious resources to generate off-the-shelf CAR-T cells. However, relatively little is known about the determinants that affect the efficient generation of CAR-T cells from healthy donor-derived peripheral blood mononuclear cells (PBMC) compared with those from the patients' own PBMC. We here examined the efficiency of CAR-T cell generation from multiple healthy donor samples and analyzed its association with the phenotypic features of the starting peripheral blood T cells...
March 22, 2024: International Immunology
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