Good news! Cancer is history (soon)!
"Greater precision for in vivo CAR T
Researchers have invented a two-vector system that uses CRISPR–Cas9 gene editing to create in vivo cancer-fighting CAR T cells without accidentally targeting other cells. Leukaemia and multiple myeloma were eliminated in the mice treated with these precision in vivo CAR T cells, while more than half of mice with sarcoma went into remission. Biotech company Azalea Therapeutics is testing the approach in monkeys and hopes to trial the treatment in people by the end of next year."
From the abstract:
"Engineered T cells, reprogrammed to express chimeric antigen receptors (CAR) or T cell receptors (TCR), have transformed cancer treatment and are being explored as therapeutics for autoimmune and infectious diseases. Enhancing T cell function through genome editing, either by disrupting endogenous genes or precisely inserting DNA payloads, has shown considerable promise. However, the ex vivo manufacturing process is lengthy and costly, limiting accessibility of these therapies. In vivo generation of CAR T cells could overcome these barriers, but current methods rely either on transient expression with limited durability, or on random integration of DNA payloads that lack specificity.
Here we demonstrate that stable and cell-specific transgene expression can be achieved through in vivo site-specific integration of large DNA payloads. We developed a two-vector system to deliver CRISPR–Cas9 ribonucleoproteins and a DNA donor template, using enveloped delivery vehicles and adeno-associated viruses, respectively. We optimized both vectors for T cell-specific delivery and gene-targeting efficiency.
By integrating a CAR transgene into a T cell-specific locus, we generate therapeutic levels of CAR T cells in vivo in humanized mouse models of B cell aplasia, and haematological and solid malignancies. These findings offer a pathway to more efficient, precise and widely accessible T cell therapies."
CRISPR makes enhanced cancer-fighting immune cells inside mice "Gene-editing technique promises a potentially safer way to create CAR T cells with a simple injection."
A gene-editing method generates immunotherapeutic CAR T cells in the body "Laboratory-engineered immune cells called CAR T cells provide effective treatment for some cancers. Progress is being made towards creating these cells in vivo." (no public access)
In vivo site-specific engineering to reprogram T cells (open access)
Fig. 1: Co-delivery of Cas9-EDV and HDRT-AAV generates TRAC-CAR T cells in vitro and in vivo.
Previous efforts to create in vivo CAR T cells have involved viral vectors (that sometimes accidentally edit ‘bystander’ cells using retroviral transduction) or lipid nanoparticles (which deliver mRNA to T cells, creating transient expression of the CAR protein). To specifically target and permanently edit T cells, the team used two vectors: a CRISPR-Cas9 gene-editing system inside ‘enveloped delivery vehicles’, and viruses that transported the DNA coding for the CAR protein.
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