The invention provides compositions and methods for adoptive T cell therapy in treating a variety of disorders including cancer, infections, and autoimmune disorders. * 1 Roberta Aliperta M.Sc.
The ectodomain is a key region responsible for the recognition of target antigens; the H/TM domains transmit antigen recognition signals to the endodomain where signaling occurs; and the endodomain is responsible for co-stimulatory signals that promote T cell survival and . Structure of different chimeric antigen receptor (CAR) generations. To address these limitations, Xyphos Biosciences - an Astellas company - created a universal chimeric antigen receptor (CAR; Figure 1 Range of possible functions with the universal chimeric antigen . Overview. The genetically modified human cells are expanded outside of the body to produce large numbers of killer T cells that can recognize and kill the dog's B cells. along with the concept of universal CAR-T cell development. Cho JH, Collins JJ, Wong WW. WO2022115864 - UNIVERSAL CHIMERIC ANTIGEN RECEPTOR-EXPRESSING IMMUNE CELLS FOR ALLOGENEIC CELL . Chimeric antigen receptor (CAR) therapy is a promising modality for the treatment of advanced cancers that are otherwise incurable. Chimeric antigen receptor (CAR) T-cells are genetically engineered T-cells with potent biocidal activity against respective target-expressing cells. Currently, T cells used in CAR therapy are mainly isolated from the peripheral blood mononuclear cells (PBMCs) of patients. The development of strategies for flexible and modular CAR T systems is accelerating, allowing for multiple antigen targeting, precise programming, and adaptable solutions in the field of cellular . Cell 2018; 173:1426.e11 . CARs consist of an extracellular binding moiety providing antigen specificity and an intracellular signaling domain derived from an activating immune receptor. doi: 10.1016/j.cell.2018.03.038. All of these issues can cause CAR T therapies to fail - either during treatment or due to relapse and antigen loss after administration.
The present invention provides a universal, yet adaptable, anti-tag chimeric antigen receptor (AT-CAR) system which provides T cells with the ability and specificity to recognize and kill target. Chimeric antigen receptor T (CAR-T) cell therapy is an emerging and effective cancer immunotherapy. The chimeric antigen receptor T (CART)-cell therapy was most recognized by its antitumor ability in relapse/refractory (R/R) hematological cancers to achieve a high complete remission rate. 2018;173(6):1421.e4116-1438.e1411. * 1 3 Malte von Bonin MD . Universal Chimeric Antigen Receptors for Multiplexed and Logical Control of T Cell Responses. Multicenter, Open-label, Adaptive Design Phase I Trial With Genetically Modified T-cells Carrying Universal Chimeric Antigen Receptors (UniCAR02-T) in Combination With PSMA Peptide Target Module (TMpPSMA) for the Treatment of Patients With Progressive Disease After Standard Systemic Therapy in Cancers With Positive PSMA Marker: 4 The first generation CAR consists of a T cell activation domain (usually including the Zeta chain of the CD3 complex) and an extracellular tumor-associated antigen binding domain. Currently, there are three types of autologous anti-CD19 CAR-T cells approved for the treatment of selected relapsed B cell non-Hodgkin's lymphomas and acute B-lymphoblastic leukemia in the Czech Republic. Universal chimeric antigen receptor (CAR) expressing T cells have great potential to democratize and improve the treatment of cancer patients worldwide.
: Chimeric antigen receptor; : CARTT () * 1 Marc Cartellieri PhD * 2 Anja Feldmann PhD * 3 Claudia Arndt M.Sc. The universal chimeric antigen receptor platform (UniCAR) is a 2-component, second-generation CAR-T platform using a CD28 costimulatory domain ().The first component is a universal CAR-T cell with a CAR that by itself does not recognize any human surface antigen but a peptide motif included in the second component, a soluble adaptor called targeting module (TM). THE PROMISE OF UNIVERSAL CHIMERIC ANTIGEN RECEPTOR T CELLS. Introduction.Chimeric Antigen Receptor (CAR) T-cell therapy is one branch of immunotherapy that is successful in treating refractory hematological malignancies 1,2.Current CAR immune cells are host-specific cells that express transmembrane proteins that activate intrinsic immune cell pathways without the traditional MHC presentation.
T cells genetically engineered to express chimeric antigen receptors (CARs) represent a promising approach in cancer immunotherapy. Chimeric antigen receptors (CARs) are artificial T cell receptors that re-target patients' T cells to specifically recognize and kill tumor cells. The SUPRA CAR is a two-component receptor system composed of a universal receptor (zipCAR) expressed on T cells and a tumor-targeting scFv adaptor (zipFv) ( Figure 1 A). Universal chimeric antigen receptors for multiplexed and logical control of T-cell responses. In some studies, up to 90 percent of children and adults with B-ALL whose disease had either relapsed multiple times, or failed to respond to standard therapies, achieved remission after . International Journal of Molecular Sciences Review Modular Chimeric Antigen Receptor Systems for Universal CAR T Cell Retargeting Ashley R. Sutherland 1, Madeline N. Owens 1 and C. Ronald Geyer 2,* 1 Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada; firstname.lastname@example.org (A.R.S. In one embodiment, the invention provides a universal immune receptor that comprises a protein or peptide tag, such as a SpyCatcher or a SpyTag moiety, bound to an extracellular hinge region, a transmembrane domain, and an . Universal chimeric antigen receptors for multiplexed and logical control of T-cell responses. Cell. However, the application of CAR-T cells is obviously hampered by the adverse effects, such as cytokines . Reasons for such potential are multiple but . Universal CARs have several potential advantages over standard CAR T cell therapy including the ability to control . Google Scholar Han X, Wang Y, Wei J, Han W. Multi-antigen-targeted chimeric antigen receptor T cells for cancer therapy. The main design principle of universal . On this basis, the second-generation CAR embeds costimulatory receptors to promote the proliferation and . T cells expressing a CD19-specific CAR Combined specific targeting of antibodies with T cell involved in immune responses, T cells can target the surface of antigens independent. Our approach is allogeneic, meaning that our UCART product candidates are made from thoroughly tested donor T-cells, unlike autologous CAR T-cell products, which are derived from individual patient . Anti-tumor activity and toxicity can be controlled by adjusting the administered adaptor molecule dosing. FIELD OF THE INVENTION. The compositions and methods relate to two chimeric antigen receptors (CARs) specific to CD33 and CDS and T cells comprising the CD33 and CDS dual-CAR. Chimeric antigen receptor (CAR)-T cell therapy has demonstrated remarkable success in the treatment of hematologic malignancies, while the success has not yet been replicated in solid tumors. Treatment of antigenically . Modular Chimeric Antigen Receptor Systems for Universal CAR T Cell Retargeting Abstract The engineering of T cells through expression of chimeric antigen receptors (CARs) against tumor-associated antigens (TAAs) has shown significant potential for use as an anti-cancer therapeutic. Our manufacturing process produces product candidates based on Universal Chimeric Antigen Receptor T-cells or, UCAR T-cells targeting cancer cells. 11:604915. doi: 10.3389/fimmu.2020.604915 REVIEW published: 10 December 2020 Universal chimeric antigen receptor (CAR) expressing T cells have great potential to democratize and improve the treatment of cancer patients worldwide. A theranostic PSMA ligand for PET imaging and retargeting of T cells expressing the universal chimeric antigen receptor UniCAR. Chimeric antigen receptor T (CAR-T) cell therapy achieved extraordinary achievements results in antitumor treatments, especially against hematological malignancies, where it leads to remarkable . Because universal CAR T cells are engineered out of third-party healthy . Engineering CAR T cells from healthy donors would solve many logistical issues, allowing for rapid treatment of patients and major reductions in manufacturing . Methods of administering a genetically modified T cell expressing the dual-CAR are described. Multicenter, Open-label, Adaptive Design Phase I Trial With Genetically Modified T-cells Carrying Universal Chimeric Antigen Receptors (UniCAR02-T) in Combination With CD123 Target Module (TM123) for the Treatment of Patients With Hematologic and Lymphatic Malignancies Positive for CD123 Two Anti-CD19 CAR-T therapies have been approved for the treatment of CD19-positive leukemia or lymphoma. Universal CARs have several potential advantages over standard CAR T cell therapy including the ability to control . Universal chimeric antigen receptors for multiplexed and logical control of t cell responses. Nevertheless, autologous CAR-T therapy has been challenging due to labor some manufacturing processes for every patient, and the cost due to the complexity of the process. * 1 4 Irene Michalk M.Sc. In a pursuit for a "universal costimulator" that is applicable to various tumors, we produced fusions of CD2 and various costimulators such as CD28, 4-1BB, ICOS, CD27 and OX-40 (Figure 1). .
Previous reports proved that the combinatorial antigen recognition strategy could improve the safety profile of CAR-T cells by targeting two different tumor-associated antigens (TAAs), one as a CAR-T targeted antigen and the . CAR T therapy has achieved encouraging results in both preclinical and clinical researches of a variety of tumors [ 7, 8, 9, 10, 11, 12, 13 ]. by Claudia Arndt, Anja Feldmann, Stefanie Koristka, Martin Schfer, Ralf Bergmann, Nicola Mitwasi, Nicole Berndt, Dominik Bachmann, Alexandra Kegler, Marc Schmitz, Edinson Puentes-Cala, Javier Andrs Soto, Gerhard Ehninger, Jens Pietzsch, Christos Liolios, Gerd . Here, we describe a novel strategy of tumor retargeting universal chimeric antigen receptor T cell therapy (TRUE-CAR T). Summary Adoptive cell therapy using chimeric antigen receptor T cells is being investigated in AML through many clinical trials. Autologous chimeric antigen receptor (CAR) T cells have expanded the scope and therapeutic potential of anti-cancer therapy. Cell. Di Stasi A, De Angelis B, Rooney CM, Zhang L, Mahendravada A, Foster AE, et al. CD2 is the receptor for CD58 that is expressed on various tumor cells. Targeting modules for universal chimeric antigen receptor expressing immune cells and use in the treatment of cancer infections and autoimmune disorders - Patent WO-2018224660-A1 - PubChem National Library of Medicine National Center for Biotechnology Information About Posts Submit Contact Search PubChem The CAR molecule typically consists of the ectodomain, the hinge (H) and transmembrane (TM) domains, and the endodomain. Clinical-grade T cells are genetically modified ex vivo to express a chimeric antigen receptor (CAR) to redirect specificity to a tumor associated antigen (TAA) thereby conferring antitumor activity in vivo. Chimeric antigen receptor (CAR)-based adoptive immunotherapy employs genetically modified T cells to express CARs. . Adicet Bio, Inc. USA Private Adicet Bio, Inc. is a privately held, pre-clinical stage biotechnology company developing novel universal immune cell therapies based on gamma delta T cells engineered with Chimeric Antigen Receptors. After almost 3 decades of development, in which renowned scientists around the world were involved, T cells genetically modified to express artificial receptors (termed as chimeric antigen receptors, CARs) have finally arrived in the clinic [for reviews, e.g., 1,2,3].Moreover, two anti-CD19 CARs (Tisagenlecleucel, Axicabtagene ciloleucel) were approved by the U. S. Food and Drug Administration . . In a first aspect the present invention provides an isolated nucleic acid sequence encoding a universal chimeric antigen receptor, wherein the receptor comprises three domains, wherein the first domain is a tag-binding domain, the second domain is a linking peptide chain including an extracellular hinge and a transmembrane domain and the third . EGFRvIII antigenic peptide (EvIII) was conjugated with DSPE-PEG-Mal and was applied to construct fusogenic nanoparticles. Universal Chimeric Antigen Receptors UCART (Universal Chimeric Antigen Receptor T-cells) are "off-the-shelf" allogeneic products, whose production can be industrialized and thereby standardized with consistent pharmaceutical release criteria, over time and from batch to batch. This study aims to use special CARs that have special structures, special systems, or are greatly improved on the basis of traditional CARs to improve the anti-tumor ability, accuracy, and safety of CAR-T cells.
Background On-target off-tumor toxicity impedes the clinical application of chimeric antigen receptor-modified T cells (CAR-T cells) in the treatment of solid tumors. Chimeric antigen receptor T cells (also known as CAR T cells) . A universal chimeric antigen receptor system having an adaptable receptor specificity component (arCAR), comprising (i) an immune effector cell having a chimeric antigen receptor comprising a first polypeptide comprising: (a) an extracellular tag-binding domain, (b) a transmembrane domain, and (c) at least one intracellular signaling domain; and (ii) a second polypeptide comprising: (a) an . A fundamental part of this work and the focus of the seminar is developing "universal" chimeric antigen receptors (CAR) that can be targeted to any cell surface antigen of interest by co-administered tumor-targeting antibodies. Switchable CAR (sCAR) T-cell establishes an immunological synapse with tumor cell by engagement of CD19 target antigen through a CD19-antigen specific exogenous Antibody-switch (Fab fragment), including a peptide neo-epitope (PNE) specifically recognized by the anti-PNE sCAR (left panel). Especially in hematological malignancies, CAR-T cells have achieved exciting results. Engineering universal chimeric antigen receptors (CARs) for cancer therapy Jason Lohmueller, Ph.D. Assistant Professor, Departments of Surgery and Immunology, University of Pittsburgh, Division of Surgical Oncology Research, UPMC Hillman Cancer Center Methods. . R Adicet is also focused on identifying and validating cancer specific targets directed to the intracellular proteome .
Both are linked via a hinge and transmembrane domain. T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and .
So far, no AML-specific antigen has been identified, requiring . J Hematol Oncol. To expand the capability of CAR T cells, here, we present a split, universal, and programmable (SUPRA) CAR system that simultaneously encompasses multiple critical "upgrades," such as the ability to switch targets without re-engineering the T cells, finely tune T cell activation strength, and sense and logically respond to multiple antigens. However, there are several limitations to current treatments and the .
Chimeric antigen receptor (CAR) -T cell therapy has become one of the hot topics in tumor immunity research in recent years. The team reports on in vitro and in vivo characterization and evaluation of the technology in a paper entitled "Universal Chimeric Antigen Receptors for Multiplexed and Logical Control of T Cell . 43 . * 1 Simon Loff M.Sc. a The core structure of a CAR, highlighting the major components of the extracellular domain, the transmembrane domain and the . approaches based on chimeric antigen receptor (CAR) T cells play an increasingly important role for cancer therapy including PCa.23-35 CARs are genetically engineered synthetic receptors consisting of (i) an extracellular binding moiety most commonly derived from tumor-specific monoclonal Abs, (ii) a transmembrane domain, and (iii) intracellular Termed universal immune receptors (UIRs), these adaptable chimeric proteins maintain a relatively similar structure to CARs but contain an extracellular adapter domain that functions as an orthogonal bridge between intracellular T cell signaling domains and a soluble tumor antigen targeting ligand (TL). Engineering T cells to express chimeric antigen receptors (CARs) has shown wide-ranging potential as a potent anti-cancer therapeutic. Universal chimeric antigen receptors for multiplexed and logical control of T cell responses. During the last decade, different centers worldwide have tested the 4 PDF Chimeric antigen receptor T-cell therapy in acute myeloid leukemia J. Koedam, M. Wermke, A. Ehninger, M. Cartellieri, G. Ehninger The first-in-clinic universal chimeric antigen receptor (CAR) T-cell therapy TruUCAR GC027 induced promising early response rates and demonstrated a manageable safety profile with no evidence of . Ann Rheum Dis genic mechanism and aetiology of RA are still A chimeric antigen receptor system that can integrate signals from multiple antigens and fine tune T cell activation in a cell type-specific manner holds promises for enhancing the safety and specificity of CAR T cell therapies for cancer treatment. The generation of 'off-the-shelf' allogeneic CAR T cell products has been a major goal in the cellular immunotherapy field. Front. The present invention generally relates to the field of immunotherapy, and more specifically to Universal chimeric antigen receptor T cells specific for CD22 (UCART22) that are engineered human primary immune cells comprising at least one edited gene, preferably a gene coding a TCR subunit and/or a CD52 gene, and a Chimeric Antigen Receptors (CAR) specific for the . An attractive way to overcome these limitations and to endow polyclonal Treg populations with a desired antigen-specificity is their engraftment with chimeric antigen receptors (CARs). Background: Chimeric antigen receptor (CAR) T cell therapy has been gradually building its position in the treatment of hematological malignancies. Immunol. Chimeric antigen receptor (CAR) T-cell therapy is an advanced personalized immunotherapy used in the treatment of many cancers. It bestows the recipient immune (commonly T) cells with enhanced anti-tumor activity, leading to the profound elimination of tumor cells and preventing the tumor relapse by promoting immune surveillance. Abstract.
Cell 173:1426 (2018). Neil Koby Reid. Chimeric antigen receptor (CAR) T cell therapy is a targeted cellular immunotherapy that uses genetically engineered T cells to specifically eliminate the antigen-bearing tumor cells [ 1, 2, 3, 4, 5, 6, 7 ]. Characteristically, CARs consist of an extracellular antigen-binding single-chain antibody variable fragment (scFv) and hinge region linked to transmembrane and intracellular signaling regions. rheumatoid arthritis patients by universal chimeric antigen receptor T cells Bo Zhang ,1,2,3 Yan Wang, 2 Yeshuang Yuan, 3 Jiaqi Sun,2 Lulu Liu,1 Dan Huang,1 Jin Hu,1,3 Min Wang, 3,4 Shengjie Li,1 Wei Song, 1 Hua Chen,4 Demin Zhou,2 Xuan Zhang 3,4 To cite: Zhang B, Wang Y, Yuan Y, et al. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Introducing co-stimulatory domains, such as CD28 . The usage of genetically engineered T-cells for treating B-cell tumor, especially B-cell acute lymphoblastic leukemia, embodies how encouraging this . CAR T cell therapies targeting CD19 and now BCMA are FDA-approved and revolutionizing treatment of refractory B cell cancers. Reasons for such potential are multiple but all stem from the source of the biological material used to produce them. The zipCAR universal receptor is generated from the fusion of intracellular signaling domains and a leucine zipper as the extracellular domain. 2019;12(1):128. Although CAR-T cell therapy is highly effective in treating . Figure 1 Switch-mediated compared to traditional chimeric antigen receptor (CAR) T-cell activation. Multicenter, Open-label, Adaptive Design Phase I Trial With Genetically Modified T-cells Carrying Universal Chimeric Antigen Receptors (UniCAR02-T) in Combination With PSMA Peptide Target Module (TMpPSMA) for the Treatment of Patients With Progressive Disease After Standard Systemic Therapy in Cancers With Positive PSMA Marker: The modified immunologic effector cell of claim 1, comprising a nucleic acid encoding a chimeric antigen receptor, wherein the chimeric antigen receptor CAR comprises an antigen binding domain, a hinge region, a transmembrane domain, a costimulatory structure, and a primary signal transduction domain. Cell 2018; 173:1426.e11-1438.e11. To address selective and persistent issues associated with RA therapy, we developed a customised therapeutic strategy employing universal antifluorescein isothiocyanate (FITC) chimeric antigen receptor T cells (CAR-T cells) combined with FITC-labelled antigenic peptide epitopes to eliminate autoreactive B cell subsets recognising these antigens . Chimeric antigen receptor T-cell clinical trials have generated impressive results in the early outcomes of CAR T-cell therapy patients with blood cancers. DOI: 10.1016/j.cell.2018.03.038. Universal Chimeric Antigen Receptors for Multiplexed and Logical Control of T Cell Responses Jang Hwan Cho,1,2James J. Collins,3,4,5,6,7,8and Wilson W. Wong1,2,9,* 1Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA 2Biological Design Center, Boston University, Boston, MA 02215, USA [Europe PMC free article] [Google Scholar] A prospective novel CART cell entity with logical operated system that simultaneously encompasses multiple critical 'upgrades', such as the ability to switch targets . The first clinical data are only just emerging with mixed results, once more proving that further research is needed. INTRODUCTION Anti-tumor activity in mice is induced only when both the universal CAR T cells plus the correct antigen-specific adaptor molecules are present.
Towards Universal Chimeric Antigen Receptor Therapy in Cancer Treatment: Current Landscape and Progress. A fundamental part of this work and the focus of the seminar is developing "universal" chimeric antigen receptors (CAR) that can be targeted to any cell surface antigen of interest by co-administered tumor-targeting antibodies. ); email@example.com (M.N.O.) Flexible Antigen-Specific Redirection of Human Regulatory T Cells Via a Novel Universal Chimeric Antigen Receptor System Author links open overlay panel Stefanie Koristka M.Sc. This process is costly, time consuming, not possible for all patients, and can have very severe off-target effects. Unfortunately, the isolation and expansion of naturally occurring antigen-specific Tregs is technically difficult, labour-intensive, and time-consuming. The engineering of T cells through expression of chimeric antigen receptors (CARs) against tumor-associated antigens (TAAs) has shown significant potential for use as an anti-cancer therapeutic. stigated with CAR-T therapy with over 60 clinical trials listed on clinicaltrials.gov. Chimeric antigen receptor (CAR) is a synthetic receptor. Universal Chimeric Antigen Receptors for Multiplexed and Logical Control of T Cell Responses Highlights A split, universal, and programmable (SUPRA) CAR system for T cell therapy SUPRA CAR can fine-tune T cell activation strength to mitigate toxicity SUPRA CAR can sense and logically respond to multiple antigens to combat relapse Applications: Cancer immunotherapy Above all, the universal CAR construction service is one of the most unique services. Chimeric Antigen Receptor (CAR) T-cell therapy is a form of immunotherapy wherein T-cells are designed to attack cancer cells, currently used most often to treat blood or lymphatic cancers. 1. Wilson Wong and co-authors introduce a unique split/universal chimeric antigen receptor (CAR) targeting system called SUPRA that affords tunable control over immune cell activity via soluble . Particle size, surface charge and stability of the nanoparticles were characterized. This type of treatment is known as adoptive immunotherapy and the cells that are infused into the patients are known as universal chimeric antigen receptor T cells (UCAR T cells). Universal Chimeric Antigen Receptor-modified AT19 Cells for CD19+ Relapsed/Refractory Hematological Malignancies The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. 2018;173(6):1426-1438.e11.