Senolytic CAR T Cell Therapy Improves Health in Aged Mice
To the degree that senescent cells in a tissue exhibit distinctive surface features, one can deploy technologies such as chimeric antigen receptor T cells to selectively destroy them. T cells will destroy whatever cell binds to the chimeric antigen receptor they are equipped with. This approach has been used with great success to treat cancers, and may also see some use in the clearance of senescent cells provided that the cost is somehow greatly reduced. At present it is a very expensive therapeutic modality, given that a patient's cells must be extracted, genetically engineered, cultured for weeks or more to expand their numbers, and then reintroduced into the patient. The use of universal cells may allow a more efficient therapy, but a gene therapy that targets only T cells is perhaps a more plausible near term approach.
Senescent cells, which accumulate in organisms over time, contribute to age-related tissue decline. Genetic ablation of senescent cells can ameliorate various age-related pathologies, including metabolic dysfunction and decreased physical fitness. While small-molecule drugs that eliminate senescent cells ('senolytics') partially replicate these phenotypes, they require continuous administration. We have developed a senolytic therapy based on chimeric antigen receptor (CAR) T cells targeting the senescence-associated protein urokinase plasminogen activator receptor (uPAR), and we previously showed these can safely eliminate senescent cells in young animals.
We now show that uPAR-positive senescent cells accumulate during aging and that they can be safely targeted with senolytic CAR T cells. Treatment with anti-uPAR CAR T cells improves exercise capacity in physiological aging, and it ameliorates metabolic dysfunction (for example, improving glucose tolerance) in aged mice and in mice on a high-fat diet. Importantly, a single administration of these senolytic CAR T cells is sufficient to achieve long-term therapeutic and preventive effects.
In body maturation of car-t cells could cut their cost (using universal cells could also cut costs):
https://www.genengnews.com/topics/translational-medicine/implants-speed-car-t-cell-processing-in-vivo-treating-lymphoma-in-mice/
I've got to wonder, would universal CAR-T cells to uPAR extend the lifespan of humans if given to them today? Could life expectancy be bumped up from 75 to 85 or 95?
Right on queue:
https://www.genengnews.com/topics/genome-editing/enveloped-delivery-vehicles-enable-targeted-genome-engineering-of-human-cells/
The allogeneic route is far more efficient.
re the marshmallow. This could be installed via a large bore needle into the subcutaneous tissue, perhaps prepped with a bit of lignocaine gel.
Anywhere with a decent blood supply. Not adipose tissue. Could be striated muscle but subcutaneous far easier.
Cheap and patient friendly.
On second thoughts-- probably would need to be into striated muscle as blood supply better there.
Rather a lot of adipose in the subcutaneous tissue.