Car we've marveled at over the years (above)

original title: Car (above)immunotherapy that we have marveled at over the years refers to the use of immunological methods, by stimulating and enhancing the body's anti-tumor immune response, and the application of immune cells and effect moleculein into the host body, in collaboration with the body's immune system to suppress or kill tumors, to break the immuno-tolerance of the treatmentOncology immunotherapy includes immunocheckpoint inhibitors, cell therapy, tumor vaccines, and immunoagobulitiesCAR-T cell therapy because of its effectiveness in treating tumors has become a hot topic of research, with the introduction of two CAR-T products in 2017, CAR-T research is a blowout-type development, a variety of deformations make people dizzy, marvel and confusion coexistNext, the mini-editor takes stock of the CAR we've marveled at over the yearsmulti-target compound CAR-T
The recurrence of B-line acute lymphoblastic leukemia in CD19CAR-T trial, and the recurrence of multiple myeloma (MM) in BCMACAR-T treatment indicate that CAR-T at single-target target has some efficacy and lack of persistence, so the design of the two-target compound CAR-T is designed to further improve the targeting of T cells and achieve greater durabilityB-cell mature antigen (BCMA) as a highly promising target for multiple myeloma, BCMACAR-T showed remarkable efficacy and also appeared BCMA plus BCMA-tumor cell recurrenceKHChen et alproposed using CS1 (CD319, slamf7) as the second target to construct BC1cCAR-T (BCMA-CS1 composite CAR-T) as a strategy for the treatment of MM with CS1 (CD319, slamf7) as the strategy for the treatment of MMBC1cCAR-T has two complete and independent receptors for multiple myeloma antigens BCMA and CS1, which, compared to single-target CAR-T cells, demonstrated targeted cytotoxicity for multiple groups in multiple mouse models using myeloma and mixed cell populations, further improving efficacy and intact in the bodyblack line for the control group, the blue line for BCMACAR-T treatment, the red line for the BC1cCAR-T treatment groupSeattle Children's Hospital opened STRIvE-01CAR-T clinical trial, using both targetEFr and CD19CAR-T cells to treat children and adolescents with recurrent or refractory non-central nervous system expression EGFR solid tumorsIt is hoped that CD19 targetsex will continue to interact with B lymphocytes in the blood to promote the amplification and persistence of EGFR-directed CAR-T cellsIn addition, there are EGFR-EGFRvIII double-target CAR-T for the treatment of glioblastoma, CLL1-CD33 double-target compound CAR-T for recurrent/difficult to treat acute myeloid leukemia, PSCA-TGF-IL4 three-target compound CAR-T for pancreatic cancerCAR-Tsolid tumors that secrete cytokinesdevelop an immunosuppressive microenvironment in the body during developmentIt is immersed in regulating T cells, tumor-related macrophages and IL-10, TGF-beta inhibitory cytokines, etc., which greatly limits the treatment of car-T cells for solid tumors, and how to improve the tumor microenvironment has been the focus of researchersthe team led by Japanese scientist Professor Koji Tamada developed the "7 x 19CAR-T" to transfer the IL-7 and CCL19 genes into CAR-T cells, which secrete IL-7 and CCL19 to summon T lymphocytes and dendritic cells to effectively immerse themselves in tumor tissue, effectively killing and killingCompared to conventional CAR-T cell therapy, the anti-tumor effectiveness of "7 x 19CAR-T" was more than four times higher, and almost 100% of the tumor mice survivedIn addition, "7 x 19CAR-T" treatment can produce a large number of memory T cells, the elimination of solid tumors after 100 days inoculated cancer cells, tumors can not formblack line for the control group, the green line for the cyclophosphamide (CPA) treatment group, the blue line for cyclophosphamide plus conventional CAR-T cell therapy group, the red line for cyclophosphamide plus 7 x 19CAR-T cell therapy group
similarly, Juno tried to develop a target to the surface of ovarian cancer cells MUC16 product JCAR020, using IL-12 to stimulate T cell activation to enhance the therapeutic effectthe development of the autonometic PD-1 antibody single-chain variable fragment CAR-Timmuno-checkpoint regulatory drug is a hot spot in recent years, and the immunocheckpoint inhibitor PD-1 monoantigen is on the altar because of its high applicability, longer sustainability after effect and smaller side effectsWhether the combination of CAR-T and PD-1 monoantigens can be combined, the Renier Brentjens team at the Memorial Sloan-Kettering Cancer Center (MSKCC) gave a positive answerThe study on the secretion of single-chain variable fragments of PD-1 antibodies CAR-T cells is published in Nature BiotechnologyCAR-T cells secrete PD-1 antibody single-stranded variable fragments (scFv), can block the immune braking mechanism of PD-1, improve the anti-tumor activity of self and other side-t cells in the tumor microenvironment, and better than CAR-T and PD-1 mono-anti-combination treatmentAt the same time, the new CAR-T cells remain in the body longer than conventional CAR-T cells, and because scFv secretion is near the tumor, it does not enter the blood circulation and produce systemic side effectsThis approach also provides a new strategy for CAR-T cell therapy, which can develop CAR-T cells that secrete different targeted scFv, such as LAG-3, TIM-3, CLTA-4, etcaccording to different needssecreting PD-1 antibody single-stranded variable fragment CAR-T cell action schematic
NKG2D receptor CAR-T natural killer cells (NK) is the first line of defense against external invasion and anti-cancer, can be non-specific direct anti-killer tumor cells NK cells rely on expression of multiple receptor functions, of which NKG2D is a member of the NKG2 family that identifies MHCI-class chain-related molecules Celyad, a Belgian cell therapy company, has developed the unique NKG2DCAR-T cell therapy (CYAD-01) Unlike other CAR-T cells currently developed, NKG2D receptors have the ability to bind to eight different ligands, which are expressed in the vast majority of cancer cells and cover 80% of blood and solid tumors The results of preclinical studies show that nKG2D-identified ligands are also expressed by the blood vessels that supply the tumor and the inhibitory cells that help the tumor escape the immune system This means that CYAD-01 can not only target and kill tumors, but also destroy the entire microenvironment and induce long-term anti-tumor-specific memory immune responses Celyad is developing cyAD-01 clinical trials for a range of hematomas and solid tumors Treatment of patients with hematoma (AML and MM) has shown good safety and tolerance Three clinical trials for metastatic colorectal cancer have also shown good tolerance for the time being, with full data expected to be completed by mid-2019 NKG2D
CAR-T regulates immunosuppressive tumor microenvironment (TME) and induces long-term antitumor-specific memory immune response
CAR-NK natural killer cells have some unique advantages over T-cells, then CAR-modified NK cells can effectively identify tumor cells, and instant lycell by releasing killer media, inducing apoptosis and other means According to this vision, Nantkwest established three technology platforms, haNK, taNK, and t-haNK, with NK cells as the core haNK (high-affinity Natural Killercell) is an engineered high affinity receptor NK cell designed to antibody mediate to enhance the killing of cancer cells Target-Activated Natural Killer Cell is an ENGINEERed nk cell (CAR-NK) that targets tumor-specific antigens on the surface of cancer cells t-haNK is an innovative combination of innate killing, antibody mediated, and CAR-NK CAR-NK in addition to the broad-spectrum tumor killing effect, its killing effect on tumor cells is immediate, after killing can release a large number of tumor antigens to stimulate other immune cells, play a long-term immunoactivation effect At the same time, CAR-NK also breaks the limits of personalized preparation, and the characteristics of equal quality and stable state make large-scale production possible In a study published in the journal CellStemCell, researchers at the University of California, San Diego (UCSD) and the University of Minnesota, , car-modified natural killer cells (CAR-iPSC-NKcell) derived from auto-induced pluripotent stem cells (iPSC) showed increased antitumor activity and lower toxicity in mouse ovarian cancer models Nantkwest's haNK, taNK and t-haNK technology platforms with NK cells as its core haNK/taNK/t-haKvs auto-body CAR-T
CAR-NKT
NKT (naturalkillerkillerT) cells are an inherent lymphocyte between adaptive and intrinsic immune cells, with t-cell receptor TCR and special t-cell sub-groups on the surface of cells CellMedica took a different approach by choosing NKT cells as a modification object, while integrating IL-15 to enhance cell amplification and durability The world's first child neuroblastoma patient has successfully accepted the company's research on the self-contained CAR-NKT therapy CMD-501 (GD2-CARNKT), an allogeneic universal target CD19 CAR-NKT is also under development CAR-T
T cells are also a class of T-cells between adaptive and inherent immunity, accounting for 1% to 5% of peripheral blood T lymphocytes, mainly distributed in mucous membranes and epithelial tissues The identification antigen of the gamma T cell has no MHC restriction, not only can kill tumor cells in a variety of ways, but also acts as an antigen-carrying cell (APC) to carry out the presentation antigen T cells are immune monitored by natural lying to various tissues, and have more potential for solid tumor therapy than alpha beta T cells AdicetBio transforms the gamma T cells into CAR-T cells, enabling them to accurately identify specific antigens, efficiently kill tumor cells, and challenge the treatment of solid tumors with the properties of gamma T cells TCBioPharm has developed four platform technologies, Omimmune, ImmuniCAR, OmmniCAR and OmniCytex, with gamma-T cells as its core OmnImmune is an unenseeded, allogeneic, radon T-cell treatment platform provided by a healthy donor ImmuniCAR is an autonomous CAR-T cell therapy platform OmmniCAR is an allogeneic CAR-T cell therapy platform OmniCytex is a cell therapy platform for stem cells as a rich cell source In the treatment of breast cancer, kidney cancer, colorectal cancer and other solid tumors and some hematoma, the treatment of common adverse reactions in the treatment process for fever, fatigue, flu-like symptoms, no serious adverse reactions occurred, CAR-T cell therapy is worth looking forward to AdicetBio's CAR-T cell production platform reference source: 1.ChenKH, WadaM, PinzKG, etal Amadchimericeceit strategy fortargeting multiplemyeloma Leukemia, 2018, 32 (2): 402.Adachi K, KanoY, NagaiT, etal.
2.IL-7andCCL19 expressionin CAR-Tcellsimproves immune cellinlinlinloand car-Tcellsurvivalinthetumor Naturebiotechnology, 2018, 36 (4):346.
3.RafiqS, YekuOO, Jackson HJ, etal Targeteddeliveryofa PD-1-blockingsc FvbyCAR-Tcellsenhancesanti-tumorefficacyinvivo Naturebiotechnology, 2018.
4.Lonez C, Verma B, HendliszA, etal Studyprotocolfor think: aglobalopen-labelphase i studytoassessthesafety and clinical activity ysofmultiple administration sof NKR-2 inpatients withmetalothacyntypes BMJopen, 2017, 7 (11):e017075.
5.https://nantkwest.com/technology/
6.https://www.
6.https://
-drug-ring-copyright-notice: This article is reproduced from Longton Capital, and if we do not wish to be reproduced by media or individuals can contact us, we will immediately delete the