FDA approves dual-switch CAR-T cell therapy into clinical

Currently,CAR-Ttreatment has been successful in some blood tumors, but in fact,cytokine release syndrome (CRS)has been regarded as the biggest impediment to CAR-T cell therapyAlthough the drug can be used prior to CAR-T cell therapy
theCRS can be used, but it cannot be controlled after CAR-T cell infusionCRS is the large number ofimmunecells are activated and proliferate after the CAR-T cell infusion in tumor patients, resulting in excessive cascade release of cytokine such as IL-6, IL-1, IL-1, TNF-alpha, IFN-alpha, GM-CSF, and eventually the formation of cytokine stormsthese cytokine-mediated hyperimmune reactions can cause patients with fever, myalgia, hypotension, breathing difficulties, clotting disorders, end-of-life organ dysfunction and other clinical manifestations, these are the most common and high incidence of car-T cells in the current clinical side effectsCAR-T treatment related toxicitypreventionstrategy, on the one hand, can be detected by CRS and neurotoxic predictive biomarkers, through intensive monitoring and timely response, on the other hand, the design of a safer CAR-T cell therapy, and the current consensus strategy is to put CAR-T on the "safety switch" , under artificial control, and in time to brake on adverse reactions before currently, companies are developing CAR-T cells that carry safety switches, such as Bellicum, Cellectis, Autolus Therapeutics, Poseida Therapeutics, Ziopharm Oncology and Precigen , Bellicum Pharmaceuticals announced that its new drug research application (IND) for HER2's CAR-T therapy BPX-603 has been approved by the U.S FDA The BPX-603 is the company's first dual-switch GoCAR-T ®, combining a total of activation switches to stimulate the MyD88/CD40 with the ® safety switch of the Caspa CIDe CID technology platform (pictured) imports molecules of specific DNA into target cells through viral vectors, enabling target cells to express CID proteins CID proteins include signal regions and binding regions, and the signal is turned off when the rimiducid molecule is not combined with the CID binding region When the binding region with the CID protein is combined into a dipolymer, the dipolymer initiates the cascade reaction of the downstream signal in fact, Bellicum is one of the leaders in this area, based on the core technology CID technology platform (chemically induced dipolymerization technology), the company developed a series of immunotherapy that significantly reduces the side effects of cytokines storms, by introducing and combining specially designed CID to car-T therapy to control the opening and closing of the signaling pathway, making the cell therapy more controllable, and thus solving the problems of individual differences, the difficulty of dose control, and the effect of severe treatment Bellicum's core technology is the CID Technology Platform (Chemically Induced DIPolymerization), on which Bellicum develops a range of immunotherapy that significantly reduce the side effects of cytokine storms By introducing and combining the specially designed CID to the signal domain, car-T therapy is added to a molecular switch rimiducid to control the opening and closing of the signaling pathway, makes cell therapy more controllable , thus solving the problems of large individual differences, difficult to control the dose, prone to serious side effects, and so on, the quality of the treatment effect is regulated it is worth noting that the company also successfully developed CAR-T cells "dual safety switches", a research paper published in 2019 two-dimensional regulation of CAR-Cell with Orthogonal Switches , Bellicum initially confirmed that this novel, adjustable dual switch system can promote CAR-T cell expansion and extend the toxicity in a drug-dependent manner GoCAR-T technology enables CAR-T cells to contain two co-stimulating signal domain activation switches GoCAR-T cells survive without antigens, proliferate under antigens, and T-cell killing function is activated only if the tumor cell and Rimiducid exist at the same time clinically approved dual-switch CAR-T BPX-603 is Bellicum's first candidate for the dual-switch GoCAR-T ®, combined with a total of myD88/CD40 activation switch and CaspaCIDe ® safety switch for the treatment of Her2-positive solid tumors -induced MyD88/CD40 (iMC) MyD88/CD40 is a signal molecule that activates and proliferates MyD88 proteins work when cells are stimulated by stress, growth factors, bacteria, or viruses, and CD40 is a co-stimulating protein found in antigen-presenting cells iMC (Picture: Bellicum) the activation and proliferation of signal molecules MyD88 proteins work when cells are stimulated by stress, growth factors, bacteria, or viruses, CD40 is a co-stimulating protein found in antigen-presenting cells, and the role of MyD88 and CD40 has previously been studied in dendritic cell therapy, and Bellicum's new technology has applied them to T-cell immunotherapy -induced MyD88/ CD40 (iMC) provides a controlled costimulation of CAR-T cells when given the dipolymer rimiducid, and enhances their proliferation and survival, as well as the activity of the anti-hematoma and solid tumor models Rimiducid (Rim, AP1903) has two symmetrical surfaces, which have a high affinity (Kd-0.1n) with the FKBP12 F36V variant (Fv), resulting in olipolymerization of iMC, and the realization of MyD88 and CD40 co-induced signal conduction The safety switch® Caspase-9 is the initiation enzyme of the apoptosis signaling pathway, which, when activated, produces a signal cascade reaction, including the activation of Caspase-3, which eventually causes apoptosis Caspase-9 can be induced by the small molecular compound CID to induce dipolymerization, thus initiating the apoptotic pathway of CAR-T cells CaspaCIDe is a of safety switching technology used to the elimination of toxic cells, mainly in the hematopoietic stem cell transplantation and TCR treatment candidates such as BPX-501, BPX-701 If the patient experiences serious side effects in the treatment, the rimiducid molecule activates the Caspase-9 signal domain on the CID molecule, eliminating all or part of the toxic cells and reducing the severe side effects in the treatment "This FDA approval is an important milestone for Bellicum to add clinical trials to evaluate our innovative GoCAR-T technology," said Rick Fair, President and CEO of Bellicum We look forward to launching the Phase 1/2 trial of BPX-603 later this year in patients with HER2-expressed solid tumors "
leader in new controlled cell immunotherapy
Bellicum focuses on the development of new controlled cell immunotherapy for the treatment of blood tumors, solid tumors, and rare inherited blood diseases, in addition to BPX-603, there are two candidates for clinical trials Bellicum's research pipeline (Photo: Bellicum) the company's development pipeline introduces the bpX-501 bpX-501 is the fastest growing cell therapy drug in Bellicum , which is mainly used hematopoietic stem cell transplant (HSCT) patients with transplanted and anti-host disease (
) The drug currently has good initial data on hapostoma stem cell transplantation Bellicum pilot product BPX-501 has achieved good early results in children's leukemia, lymphoma and hereditary hematopoietic stem cell transplantation treatment haposcostosis stem cell transplantation is often associated with GVHD risk, of which the risk of hapmy semi-phase transplantation GVHD is greater T-cells are often removed in haploid semi-phase transplantation treatment to reduce the risk of transplant resistance to host disease, but the lack of donor T-cells can lead to an increase in infection in transplant patients Joining BPX-501 can reduce infection rate, shorten hospital stay, and achieve better treatment results The BPX-501 uses proprietary CaspaCIDe safety switching technology to import rumiducid activators to control the elimination of toxic T cells, successfully solving the problem of doctors not wanting to perform monoploid semi-phase transplants with high GVHD risk the European Commission and the U.S Food and Drug Administration (FDA) have qualified for orphan drugs for bpX-501 and rimiduced combination therapy BPX-601 BPX-601 drugs currently carry out the stage 1 treatment plan for the treatment of solid tumor CAR-T immunotherapy
It is a candidate for the company's GoCAR-T series of drugs to treat a variety of malignant solid tumors that express prostate stem cell antigens (PSCA), including prostate cancer, pancreatic cancer , bladder cancer, esophageal cancer and stomach cancer bpX-701
BPX-701 is a candidate drug for immunotherapy of acute myeloid leukemia (AML) and myelogenesis abnormal syndrome (MDS) TCR cells, targeting melanoma-specific antigens , Bellicum's proprietary "safety switch" technology provides a good solution to the current difficulties encountered in the development of cell therapy, and we look forward to its follow-up clinical progress, as soon as possible for many patients to bring a safe and effective treatment program Medical McKay Source: Medical