Scientists from Johns Hopkins University have found a way to improve immunotherapy with magnetic nanoparticles. The researchers used magnetic cells with artificial antigens to extract tumor-specific white blood cells. From that enriched starting culture, a 1000-fold expansion of human tumor-specific T cells was achieved in 1 week. The work was published in ACS Nano.
Our immune system uses white blood cells -T cells- against cancer. T cells are originally inactive in the system, waiting for a specific antigen from a virus, bacteria or tumor. The problem is that naive T cells are very rare in the blood. An additional problem is that T cells need to divide fast an reach high numbers to be able to fight the tumor cells. Adoptive immunotherapy (AIT) solves that problem by collecting T cells from the patient, activating them against a specific target, replicating and reintroducing them. However, AIT is expensive and complex.
Cost-effective “Enrichment + Expansion” of specific T cells
In previous projects, Schneck’s group had been experimenting with artificial antigen-presenting cells (aAPCs). They mixed aAPCs with naive T cells, which resulted in T cells becoming active against cancer cells that presented the same antigen as the aAPCs. Also, they saw activation is quicker in the presence of a magnetic field. Magnets bring aAPCs and receptors closer, which activates T cells against their target and makes them proliferate.
Schneck and his colleagues mixed human (or mice) blood with magnetic aAPCs bearing antigens from tumors, then they ran the mix through a magnetic column. The T cells that acquired specificity against the antigen where bound to the magnetic aAPCs, which were bound to the column. A simple elution discarded the undesired T cells and enriched the specific ones. Posterior cell culturing increased the cell count to levels that allow therapeutic use.
This “Enrichment + Expansion” technique can be very powerful for cheaply generating large numbers of specific T cells, and will be tested in the future against several other antigens, with the possibility of starting clinical trials soon.