Miltenyi Biotec GmbH | Date: 2016-08-31
Miltenyi Biotec GmbH | Date: 2015-04-23
The present invention provides a process for generation of genetically modified T cells, T cell subsets and/or T cell progenitors comprising the steps: a) providing a cell sample comprising T cells, T cell subsets and/or T cell progenitors b) preparation of the cell sample by centrifugation c) magnetic separation of the T cells, T cell subsets and/or T cell progenitors d) activation of the enriched T cells, T cell subsets and/or T cell progenitors using modulatory agents e) genetic modification of the T cells, T cell subsets and/or T cell progenitors f) expansion of the genetically modified T cells, T cell subsets and/or T cell progenitors in a cultivation chamber g) washing of the cultured T cells, T cell subsets and/or T cell progenitors characterized in that all steps are performed in a closed and sterile cell culture system.
Miltenyi Biotec GmbH | Date: 2015-03-05
The invention is directed to a process for sorting target cells and non-target cells from a sample by a cell sorting valve microfabricated on a surface of a silicon substrate, with microfabricated channels leading from the cell sorting valve, wherein the cell sorting valve separates the target particles from non-target material; a disposable cartridge containing a sample reservoir, a sort reservoir and a waste reservoir; wherein the sample is provided in a buffer comprising nuclease.
Miltenyi Biotec GmbH | Date: 2017-03-08
The invention is directed to disposable for electroporation of cells, comprisinga fluid compartment in an interior of the disposable;a first fluid port for providing cell suspension to the fluid compartment, and a second fluid port for delivering a fluid comprising at least one compound to be electroporated into the cells to the fluid compartment;a first electrode and a second electrode disposed in the fluid compartment;at least one exit port which delivers the fluid from the fluid compartment wherein the first and second fluid port have a fluid communication to a mixing channel which has a fluid communication to the fluid compartment.
Miltenyi Biotec GmbH | Date: 2017-03-08
The present invention provides a method for in-vitro culturing and expanding natural killer (NK) cells in a cell culture medium comprising a population of NK cells, the method comprising a) adding an effective concentration of interleukin-21 (IL-21) at the beginning of the culturing process to said medium, b) adding repeatedly an effective concentration of interleukin-2 (IL-2) and/or interleukin-15 (IL-15) to said medium, and c) adding repeatedly feeder cells or membrane particles thereof to said medium, wherein said feeder cells are B cell derived which are EBV immortalized; and wherein said expansion of NK cells in said cell culture medium is maintained for at least 3 weeks.
Agency: European Commission | Branch: H2020 | Program: IA | Phase: ICT-28-2015 | Award Amount: 10.29M | Year: 2016
Photonics is essential in todays life science technology. PIX4life will mature a state of the art silicon nitride (SiN) photonics pilot line for life science applications in the visible range and pave the way to make it accessible as an enabler for product development by a broad range of industrial customers. We aim at 1) establishing a validated CMOS compatible SiN technology platform in the visible range for complex densely integrated photonics integrated circuits (PICs), 2) developing a supply chain to integrate mature semiconductor laser sources and CMOS detector arrays with the SiN PICs on the basis of technologies that are scalable to high volume, 3) establishing appropriate design kits and tools, 4) demonstrating the performance of the pilot line for well-chosen life science applications in the domain of vital sensing, multispectral sources for super-resolution microscopy, cytometry and 3D tissue imaging, 5) setting up the logistics for multi-project-wafer (MPW) access to the pilot line. Integrated photonics has demonstrated that optical functions can be realized in a more compact, robust and cost-effective way by integrating functionalities on a single chip. At present industrialization is limited to telecom applications at infrared wavelengths. The field of life sciences is heavily dependent on bulky and expensive optical systems and would benefit enormously from low cost photonic implementations. However this field requires a visible light PIC-technology. Proof of concept demonstrations are abundant, but pilot line and manufacturing capacity is limited, inhibiting industrial take up. PIX4life will drive the future European RTD in visible photonic applications for life sciences by bridging technological research (via participation of 2 academic and 2 research institutes) towards industrial development (via participation of a foundry, two large companies and 9 fabless SMEs, either technology suppliers or life science end users).
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-13-2014 | Award Amount: 7.57M | Year: 2015
Immune responses are initiated by antigen presentation mediated by dendritic cells (DC). There is a minority subset of DC highly specialised in starting up cytotoxic T lymphocytes able to kill tumor cells. PROCROP aims to develop in three pilot clinical trials a suitable individualized cancer vaccine technology for castration resistant prostate cancer and metastatic cancer of the ovary that would complement currently available therapies to increase efficacy. The project applies recent compelling knowledge on the identity of the main antigen-presenting DC subsets for vaccine elicitation of cytotoxic T lymphocytes endowed with the ability to seek and destroy tumour cells (such immune mechanism is termed crosspriming). This unique opportunity for superior DCs for immunotherapy comes from the fact that Miltenyi, a successful European biotech company, has the necessary proprietary reagents (anti-BDCA-3 monoclonal antibody and immunomagnetic selection technology), as well as the expertise to clinically develop a strategy of DC isolation and short-term cell culture for immunotherapy. From the point of view of the tumor antigens, processed autologous tumor material will be mixed with defined common tumor antigens in the form of recombinant proteins. This novel combination will permit stronger and broader antitumor immune responses and more accurate monitoring of the ensuing immunity against the tumors. These features should make the novel DC vaccine more efficacious than the currently US-approved DC vaccine PROVENGE and other DCs preparations undergoing trials, such as those derived from monocytes. Three of the leading groups in immunotherapy of cancer in Europe would join forces to develop this individualized cell therapy technology in clinical trials for two highly prevalent and unsatisfactorily managed malignant conditions. Industrial partnership provides the unique advantage of producing a rigorously standardized product for eventual multicentre trials.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-14-2015 | Award Amount: 7.47M | Year: 2016
Severe combined immunodeficiency (SCID) is a devastating rare disorder of immune system development. Affected infants are born without functional immune systems and die within the first year of life unless effective treatment is given. Treatment options are limited to allogeneic haematopoietic stem cell transplantation and autologous stem cell gene therapy. Over the last 15 years, gene therapy for two forms of SCID (SCID-X1 and ADA SCID) has shown significant safety and efficacy in correcting the immunodeficiency and allowing children to live normal lives. Proof of concept of gene therapy for 3 other SCID forms has also been shown by members of the proposed SCIDNET consortium and is ready for translation into clinical trials. We are therefore in a position whereby, over the next 4 years, we can offer gene therapy as a curative option for over 80% of all forms of SCID in Europe. Importantly for 1 of these conditions (ADA SCID) we will undertake clinical trials that will lead to marketing authorisation of the gene therapy product as a licensed medicine. In addition, we will investigate the future technologies that will improve the safety and efficacy of gene therapy for SCID. Our proposal addresses an unmet clinical need in SCID, which is classified as a rare disease according to EU criteria (EC regulation No. 141/2000). The proposal also addresses the need to develop an innovative treatment such as gene therapy from early clinical trials though to a licensed medicinal product through involvement with regulatory agencies and is in keeping with the ambitions of the IRDiRC. The lead ADA SCID programme has Orphan Drug Designation and clinical trial design is assisted by engagement with the European medicines Agency. The ADA SCID trial will act as a paradigm for the development of the technologies and processes that will allow gene therapy for not only SCID, but also other bone marrow disorders, to become authorised genetic medicines in the future.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-16-2015 | Award Amount: 5.99M | Year: 2016
Chimeric antigen receptors (CARs) are artificial surface receptors that can be introduced into somatic cells by genetic engineering and that act as recognition molecules like antibodies or T-cell receptors. In this respect, CARs are increasingly used for cellular therapy to redirect T-cells specifically towards killing of cancer cells. Recent success stories of cancer therapy with CAR modified T-cells have raised enormous scientific and public expectations to cure severely ill patients. However, there are still many obstacles to overcome for translation into clinics because the technology for GMP-compliant manufacture of genetically modified cellular products is extremely complex and expensive. Moreover, CAR therapy needs to be improved with respect to off-target activity, safety and potency. Consequently, the envisaged project is overall aiming at a particular technological breakthrough in cellular cancer therapy by delivering a comprehensive CARAT platform explicitly tailored for automated, easy-to-handle and cost-efficient manufacture of CAR-modified ATMP. Specifically, we aim: (a) to implement unique next-generation cell processing tools like the CliniMACS Prodigy (b) to develop advanced enabling technologies to obtain more effective and safer cellular products by improved gene delivery and innovative CARs design (c) to assemble tools and technologies towards an integrated CARAT process for automated GMP-compliant manufacture of gene-modified T-cells (d) to demonstrate proof-of-concept and regulatory compliance (e) to disseminate broadly applicable, simplified CAR T-cell technologies In summary, our vision is to overcome current hurdles for translation of cellular therapies and to elevate them to the next level of standard-of-care thus serving patients with so far incurable solid tumours and hematologic malignancies. Thereby, we will empower Europe to become a global leader in the development and commercialisation of CAR T-cell tools and technologies.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.1.4-1 | Award Amount: 7.86M | Year: 2014
Despite progress in producing beta cells from human pluripotent stem cells (hPSCs) in recent years, full differentiation cannot be obtained in vitro. The HumEn project hypothesises that a fundamental understanding of the coupling between endodermal progenitor expansion and differentiation is relevant for elucidating how to a) generate glucose-responsive beta cells from hPSCs in vitro, and b) generate sufficient number of beta cells to meet future clinical needs in cell therapy in diabetes. Thus, the overall aim of HumEn is to identify, understand, and expand human endodermal progenitors as a consistent and renewable source of cells for pancreatic beta cells differentiation. We will focus on precursors from two stages of pancreatic differentiation; anterior definitive endoderm (ADE) and pancreatic endoderm (PE) progenitors, providing mechanistic insight into the signalling pathways and downstream targets that control their expansion and functional maturation into human beta cells. Rigorous in vitro (regulated insulin-release) and in vivo (protection against experimentally induced diabetes in mice) testing of insulin-producing cells will ensure a functional end product. The consortium proposes to address these problems by a unique combination of models and experimental approaches, including genetic, surface/biomaterial screens (3D), and cell surface antibody screens as well as cell signalling-to-transcription factor/chromatin effectors. In the end, HumEn aims to deliver a reliable and scalable protocol for directed differentiation of hPSCs into bona fide beta cells. The results of the project will not only provide answers to fundamental questions, but also deliver new concepts and knowledge of general importance for coordination of cell cycle progression and regulation of cell fate specification in stem cells/progenitors. HumEn is highly innovative and carries excellent potential for translational output.