Revolutionizing Brain Tumor Treatment: DDE's Commitment to Advanced CAR-T Cell Manufacturing
Brain tumour is a global health issue, ranking 19th?in the list of most frequent malignancies and 12th?in terms of cancer mortalities as per the Global Cancer Observatory (GLOBOCAN). A tumour impairs the brain’s capacity?to control over most bodily functions, impacting sensations, thoughts, memory etc. and exposes the patient to emotional and financial trauma, poor quality of life and in severe cases death. The broad term “Brain tumour” encompasses a plethora of cancers and is classified into primary (cancers that originate within the brain) and secondary (also termed as metastatic, these originate in other parts of the body and later on spread to the brain). Primary tumours are further categorised into glial tumours or gliomas that show presence in glial cells (e.g. astrocytomas, oligodendroglial tumours, glioblastomas) and non-glial tumours that develop in blood vessels of the brain, nerves, meninges etc. (e.g., meningiomas, craniopharyngiomas, pituitary tumours). The survival rate in the case of brain tumours is comparatively very low when compared to other known cancers. Conventional treatment options include surgery, radiosurgery, radiation therapy, chemotherapy and haematopoietic stem cell transplantation. These treatments call out for a wide range of toxicities due to the sensitivity of the organ.
The need for an effective cell therapy that can respond dynamically to changes ex vivo and in vivo without leaving long-lasting side effects has led to the rise of Chimeric Antigen Receptor cell (CAR-T cell) therapy, specifically targeting tumour-specific antigens by harnessing the immune system. These genetically engineered cells cause T cells to attack specific cancer cells causing a breakthrough in the field of personalised cancer treatment. CARs are synthetic immunoreceptors and typically consists of an extracellular antigen-binding domain, hinge region, transmembrane domain, and intracellular T-cell signalling domain. The antigen-binding domain interacts with the target antigen and is made of monoclonal antibodies’ variable heavy (VH) and variable light (VL) chains, connected with short linker peptides to form a single chain variable fragment (scFv). The scFv portion is surface antigen-specific allowing CAR to activate the cell upon recognition of the target antigen.
Regulatory approvals for CAR T cells for the treatment of multiple myelomas, lymphomas, and leukaemia have accelerated research in solid brain tumours which showed poor response earlier due to the heterogeneous population of tumour antigens, blood-brain barrier, immunosuppressive tumour site environment. Rigorous research in the field of CAR T cell therapy and promising results underline the fact that CAR T cell therapy holds great potential to emerge as a novel treatment modality for brain tumours. The advantages of CAR T cells include modular design (that can be expanded ex vivo and then administered in very large quantities to patients) and lack of MHC antigen presentation rendering it a good candidate for cancer therapy.?Optimal CAR design is highly dependent on antigen‐ and tumour-specific properties and initialises with collection of the patient’s peripheral blood mononuclear cells (PBMCs). These cells are transduced (lentiviral or retroviral) with the CAR transgene, the activated T cells are then stimulated by the engagement of their T Cell Receptor (TCR) and costimulatory receptors and further expanded ex vivo in bioreactors.
Bioengineering approaches are greatly needed to improve the safety, efficacy and scalability of CAR T cell manufacturing and improvement the activation process via customizable ligand-presenting scaffolds. Another major step that needs attention is the expansion of the population of T cells available for transduction or infusion to the patient. Fully automated closed GMP-compliant systems ensure a precise expansion process in approximately ten days. Ligand-functionalized surfaces that allow bead-free expansion and thereby reduce cell aggregation and shear stress can be adopted.
DDE is all set to cater for the panorama- equipment as well as technical expertise needed for manufacturing highly effective CART cells in a limited timespan using our vast experience in the field of biopharma manufacturing. We would like to implement quality-by-design-based improvements and incorporate PAT, and automation to conventional CART cell manufacturing. We wish to provide all support in development and expansion of non-immunogenic allogenic T cells which could significantly reduce the therapy cost making it accessible to all. Advances in these novel immunotherapies would lead to a new generation of CART cell therapies offering new life and hope to brain tumour patients and shedding a beam of light into their lives.
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Biotechnology Industry Research Assistance Council (BIRAC) National Cancer Institute (NCI) European Federation for Cancer Images (EUCAIM) Cancer Tech Accelerator Cancer Research UK (CRUK) NCI Center for Cancer Research NCI Division of Cancer Control and Population Sciences American Cancer Society IIT Bombay ImmunoACT The Leukemia & Lymphoma Society Central Drugs Standard Control Organization
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5 个月Great to know this. Kudos ??