Immunotherapy requires the manufacture and expansion of an activated T cell population. Adoptive cell transfer therapy is a promising method, utilizing a patient’s own cells and expanding them in vitro before re-introduction. Activation of T cells requires antigen presenting cells such as dendritic cells, which are capable of interacting with and stimulating the T cells. Obtaining these cells can be costly and time-consuming. As such, researchers at Yale University have come up with a way to present antigen fragments to T cells using a combination of carbon nanotubes and magnetic nanoparticles.
Carbon nanotube-polymer composite
Carbon nanotubes were chosen in part because of their aspect ratio, which facilitates a clustered presentation of attached molecules. Biotinylated T-cell stimulatory signals (e.g., MCH-I, anti-CD28) were bound to neutravidin molecules adsorbed onto the surface of carbon nanotube bundles. Nanoparticles, composed of magnetite and the T cell growth factor IL-2 encapsulated within biotinylated poly(lactide-co-glycolide) (PLGA), were also bound to the nanotubes, thus enabling magnetic separation of the resulting carbon nanotube-polymer composites (CNPs) from T cells.
The effects of the CNPs were tested on isolated mouse T cells. After 2 weeks, the cell population was found to have expanded approximately 200-fold, significantly more than that observed with other antigen presenting platforms, while requiring a thousand-fold less IL-2. The resulting population of T cells delayed tumor growth when re-introduced into a mouse subject. Subsequent evaluation of the tumor tissue revealed lymphocyte infiltration and apoptosis. The CNPs also proved capable of expanding human T cells, increasing a specific population to a greater degree than that observed with human dendritic cells.
Future implications
As the authors of the study are quick to point out, one of the limiting factors in immunotherapy is cost. Because CNPs are more specific, more stable, and require significantly less cytokine, they may significantly reduce the cost associated with generating a specific T cell population. The presented antigen can be optimized to induce the proliferation of cytotoxic T cells for a number of applications, including cancer immunotherapy and treating chronic infections.
A full report of the findings is available in “http://www.nature.com/nnano/journal/v9/n8/full/nnano.2014.154.html.”
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