Artificial Cells Boost T Cell Production

Traditionally, there have been only two therapies for cancer patients: the free drug approach, whereby patients are dosed with specific drugs that try to target cancerous cells more than normal cells, and active immunotherapy, in which immune cells are stimulated specifically.

A third treatment, adoptive immunotherapy, has recently joined the battle. In adoptive immunotherapy, blood is drawn from the patient and T cells from that blood are proliferated, or expanded, outside the body. The expanded T cells are then re-injected to fight the cancer.

According to Tarek Fahmy, Assistant Professor of Biomedical Engineering and Chemical Engineering, this process provides an excellent way “to educate the immune system against cancer.” He cautions, however, that “this method is not as ubiquitous as the other two as it requires that healthcare providers have a highly specialized technical background, as well as the knowledge necessary to expand T cells to a large enough number and in a reliable way against specific cancer cells.”

Another complication has arisen because current adoptive immunotherapy techniques calls for expanding the patient’s own dendritic cells ex vivo. Dendritic cells, which process antigentic material and present it to T cells and B cells, are difficult to isolate because different individuals have different quantities of these cells. Thus, because dendritic cells are not a reliable source of expansion, growth of adoptive immunotherapy has been slow.

In an effort to work around these issues, Fahmy and Erin Steenblock, a graduate student in Engineering and Applied Science, have created their own artificial antigen presenting cell (aAPC) as an alternative therapy. Their aAPC can increase the numbers of the patient’s own T cells specific to cancer cells in vivo and ex vivo.

In addition, because Fahmy and Steenblock’s aAPCs come in a powder form, they can be stored for at least a week when refrigerated. Fahmy envisions a future when pharmacists can fill patients’ prescriptions for aAPC from bottles on a shelf and they can be as accessible as aspirin.

“Imagine rolling spaghetti noodles into a disorganized ball, adding small meatballs inside while creating it,” says Fahmy about the aAPC platform. The “noodles” are poly(lactide-co-glycolide) (PLGA), a biodegradable FDA-approved polymer system incorporated into sutures since the 1970s. The “meatballs” are cytokines, specifically interleukin-2 (IL-2), which stimulate the growth and differentiation of T cells.

PLGA is hydrolysable and therefore dissolves on contact with water. Once inside the body or in aqueous mediums, cytokines begin diffusing immediately and can quickly activate the T cells. The release of the cytokines from the aAPC is sustained and steady, allowing for the maximum increase of T cells.

The aAPCs also include surface receptors to bind specific T cells and costimulators mimicking those in the human body to maximize effectiveness. This platform mimics the body’s natural dendritic cells, which normally initiate and regulate the immune response. Surface receptors on dendritic cells bind T cells and activate cytokines to stimulate further T cell proliferation.

Fahmy’s and Steenblock’s aAPCs similarly increase the numbers of T cells specific to cancerous cells, thus enhancing the immune response that fights cancers, viruses, and bacterial infections. More importantly, their aAPCs specifically enhance killer-T cells which directly attack cancerous cells, although it is unclear why they do not enhance numbers of helper T cells.

However, this exciting development has limits. It is fairly expensive because it is tailored to individual patients. More importantly, the dearth of knowledge regarding antigens presented by cancerous cells presents a sizeable constraint.

According to Fahmy, “We’re back to the basic science, because we don’t want to amplify the wrong T cells. Once the proper cancer antigens are known, they can be easily attached to the surface of the particle.”

Nonetheless, within five to ten years Fahmy and Steenblock’s new platform should be approved for use. Fahmy predicts that their technology will be used first for very specialized cases, but once their aAPC is established as a proven method, he expects it will expand to more general applications.