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from the hopefully-them-tcells-don't-fall-off-that-scaffold dept.
Cellular therapy hasn't had much success in fighting solid tumors, partly because it's been difficult to deliver anti-cancer T cells to the tumors.
A strategy developed by researchers at Fred Hutchinson Cancer Research Center could help. The team equipped a synthetic scaffold loaded with cancer-fighting T cells and a mix of nutrients to keep the cells healthy and primed to attack cancer.
The study, to be published April 24 in The Journal of Clinical Investigation, revealed that the scaffold loaded with T cells shrank tumors in mouse models of pancreatic cancer and melanoma more effectively than T cells that were delivered via injection.
"The key to our scaffold is that it's not just a structure," said Fred Hutch's Dr. Matthias Stephan, the study's senior author and an expert in developing biomaterials. "The components we've engineered into these scaffolds include an optimal mix of stimulating factors and other ingredients that allow the T cells to survive and proliferate and to maintain a sustained fight against cancerous cells."
In the study, the researchers equipped the scaffold with chimeric antigen receptor, or CAR T cells, which are engineered in the lab to seek out proteins that are specific to cancerous cells and then destroy the cells.
(Score: 4, Informative) by Joe on Friday April 28 2017, @01:17AM
The research group loaded a silica sponge with CAR T cells and a type of molecule that will strongly induce immune responses (an adjuvant that stimulates the STING pathway) and implanted it in close proximity to the tumor. The sponge also is loaded with antibodies that will help activate any T cells that interact with it.
The idea of this approach is that there will be an initial clearance of most tumor cells by the CAR T cells, the adjuvant will help prevent the T cells from getting de-activated and will antagonize tumor supportive immune cells (such as macrophages), and the activating antibodies will support other non-CAR T cells eliminate remaining tumor cells.
The real problem limiting CAR T cell therapies is the lack of tumor-specific antigens. The problem of CAR T cells getting de-activated can be easily solved through genetic manipulation. The reason why the earlier CD19-targeting CAR T cell therapies have been so effective was because all the tumor cells contained CD19 antigens without any selective pressure (immunoediting) to delete them.
- Joe
Paper Link: https://www.jci.org/articles/view/87624 [jci.org]
CAR T cells: https://en.wikipedia.org/wiki/Chimeric_antigen_receptor [wikipedia.org]
STING: https://en.wikipedia.org/wiki/Stimulator_of_interferon_genes [wikipedia.org]
Adjuvant: https://en.wikipedia.org/wiki/Adjuvant [wikipedia.org]
Tumor-associated macrophages: https://en.wikipedia.org/wiki/Tumor-associated_macrophage [wikipedia.org]
Tumor-specific antigens: https://en.wikipedia.org/wiki/Tumor_antigen [wikipedia.org]
Immunoediting: https://en.wikipedia.org/wiki/Immunoediting [wikipedia.org]