AACR: Better than traditional CAR-T, multi-gene CAR-T based on non-viral vector systems shows better amplification and persistence of medical mammoths.

Notice: users who successfully sign up for the Meditech 2020 biopharmaceutical Innovation Technology Conference (click now to view the agenda of the conference) will have the opportunity to receive a free copy of car-t cell therapy Industry Research Report 2020 v2.1 produced by Xingyao Research Institute of Meditech media in 2020.limited to 2000 copies!!! This novel coronavirus pneumonia is welcome to share. It is necessary to authorize the June 24, 2020 / eMedClub News/-- AACR global hospital to be affected by the new global crown pneumonia. The American Cancer Research Association (AACR) cancelled the scheduled annual meeting in late August this year, and decided to hold an online meeting on April 27, 2020 and June 22nd -24 respectively.precigen, which focuses on the development of innovative gene and cell therapy, recently announced at the second AACR conference its innovative study prgn-3005 ultracar-t? In patients with advanced recurrent platinum resistant ovarian cancer, fallopian tube cancer or primary peritoneal cancer.prgn-3005 is an autologous car-t therapy that expresses three gene products at the same time, so as to achieve a uniform car-t cell therapy: 1) specifically targeting mucin 16 (muc16) is over expressed in more than 80% of ovarian tumors, but limited in healthy tissues; 2) membrane binding IL-15 (mbil15) enhances the persistence of ultracar-t in vivo and better maintains the preferred stem cell like memory phenotype; 3) a kill switch that can eliminate car-t cells when necessary, aiming to improve treatment control.prgn-3006 and prgn-3005 are polygenic car-t therapies based on precigen's sleeping beauty technology platform (sb system).using the platform's advanced non viral delivery system, it co expressed chimeric antigen receptor, mbil15 and a targeted indication switch to achieve precise control. Both gn300br / > and gn300br / > have entered the clinical stage.recommended reading (including the overview of cell therapy based on non viral vector gene delivery technology): precigen announced that ultracar-t therapy based on sleeping beauty system has entered the first phase of clinical practice. Mai Meng reports that "Sleeping Beauty" car-t therapy has completed the first solid tumor patient administration, and cell therapy based on transposon technology has obvious advantages- Tultracar-t platform has the following significant advantages: the use of multi gene vector for non viral gene transfer, in order to express a variety of effector genes, thus having better tumor targeting specificity and control, and eliminating the need for viral vector.the co expression of mbil15 can enhance the specificity and persistence of immune activation of ultracar-t cells and help to solve the problem of T cell failure, which is also a common problem in car-t therapy.the control switch can control T cells and improve the potential safety.using proprietary non viral gene transfer technology, ultracar-t cells can be rapidly produced without in vitro proliferation, thus greatly reducing the waiting time of patients.the preclinical data of prgn-3005 announced this time demonstrate the specificity and effectiveness of the rapid production of prgn-3005 ultracar-t cells in the treatment of ovarian tumors.specifically, compared with traditional car-t cells, prgn-3005 exhibits a stem cell like memory phenotype, significantly improves survival even in the absence of exogenous cytokines, and lacks autonomous proliferation in vitro without muc16, demonstrating the benefits of mbil15 on phenotype and persistence of ultracar-t cells.in this study, a single application of prgn-3005 showed obvious superiority in the amplification of ultracar-t and the preferred memory phenotype in vivo, and had remarkable excellent efficacy, resulting in no tumor in all prgn-3005 treated mice.three months later, these tumor free mice were challenged with ovarian tumor again to simulate tumor recurrence, and the tumor burden could be eliminated without additional prgn-3005 ultracar-t treatment.these data indicate that ultracar-t cells have the ability to survive in vivo for a long time, prevent car-t cell failure, establish a lasting anti-tumor response, and have the ability to continue to respond to tumor.in addition, this study also demonstrated that prgn-3005 cells can be activated by killing switch, and the antibody can be selectively and effectively eliminated by ADCC.potential strategies for the treatment of ovarian cancer (solid tumor). Ovarian cancer is the most lethal gynecological cancer. Nearly 300000 women are diagnosed with ovarian cancer every year, including about 22000 women in the United States. because early ovarian cancer usually has no obvious symptoms, it is often diagnosed at the late stage of cancer spread (e.g. to the liver or lungs). the five-year survival rate depends on the stage and type of ovarian cancer, and the survival rate of advanced cancer spreading far away from the body is reduced. car-t cells have achieved more successful clinical results in the field of hematological malignancies. however, similar responses have not been achieved for solid tumors. traditional methods of manufacturing car-t cells include the use of virus vectors and in vitro cell expansion for several weeks in a centralized manufacturing facility to achieve the number of relevant cells required by clinical practice, which leads to phenotype failure of car-t cells, high manufacturing costs and delayed treatment. in contrast, precigen's ultracar-t platform is based on a non viral multi gene delivery system, combined with a rapid and decentralized production process, without in vitro amplification. after the blood is drawn to isolate the patient's own T cells, the non viral gene transfer will be completed in the cGMP facility of the medical center that night; ultracar-t cells can be injected into the patient the next day. Dr. Helen sabzevari, President and CEO of precigen, said: "we are pleased to be able to share preclinical data from prgn-3005, which led to ind approval and the start of phase I studies. our preclinical results show that prgn-3005 ultracar-t, administered one day after non viral gene transfer, has better antitumor efficacy and persistence than traditional car-t cells, which provides a broad prospect for the treatment of ovarian cancer. we look forward to sharing the first clinical data of prgn-3005 in the second half of 2020. "the transposon technology favored by Dr. Carl June has been obtained. At present, the main way of car-t treatment is to modify T cells by gene technology and reproduce in vitro. however, most of the cell therapy that needs gene modification or gene therapy that takes gene transfer and modification as the treatment method is currently based on virus vector. however, the manufacturing process of viral vectors is complex, expensive and strictly controlled; in terms of supervision, it is difficult to meet all aspects of cGMP in the early stage of clinical trials. in addition, there are challenges in the evaluation of the efficacy and safety of viral vectors and the transportation. therefore, the production and supply of vectors may be one of the biggest constraints in the field of cell and gene therapy. however, the goal of non viral vector gene delivery based on transposon technology is to change the mode of gene delivery and eliminate the need to culture (T) cells in vitro in cell therapy, which will accelerate treatment and reduce costs. "Sleeping Beauty (sb) transposon system is a member of Tc1 / mariner transposon superfamily, which has been silent for more than 10 million years. It was not until 1997 that ivics revealed its transposable activity. transposition sequence and transposase are similar to the "cut and paste" method. The transposon vector system can carry a segment of exogenous DNA sequence during transposition, which can be used in transgenic, gene screening, gene therapy and other fields with good application prospects. it can transpose in most vertebrate cells cultured in vitro, and mediate the stable integration and long-term expression of foreign genes. ziopharm oncology is also one of the main forces committed to the development of cell therapy such as car-t based on this technology. recently, Dr. Carl June, a pioneer in car-t therapy, joined ziopharm oncology as chairman of the company's newly established scientific advisory board (SAB). in a press release issued by ziopharm, Dr. Carl June will provide strategic advice to ziopharm with his pioneering experience in gene therapy and T-cell therapy to guide the development of innovative technologies and immunotherapy for the treatment of more solid tumor patients. this proves once again the great potential of this technology! Recommended reading: in the development of TCR / car-t and gene therapy, ziopharm invited Carl June as chairman of the Scientific Advisory Committee. Mai Meng revealed that it focused on four hot biomedical fields, including tumor immunity, new antibodies, stem cell regeneration medicine and gene therapy, and 2020 bpit Biopharmaceutical innovation and technology conference will be held in Nanjing International Youth Culture Center on July 19-21, 2020! Click the picture above to view the agenda of the conference