Researchers have attached capsules containing the drug SN-38, a relative of irinotecan, to T cells. When infused into mice with a cancer similar to Burkitt lymphoma, the T cells entered the spleen, lymph nodes, and bone marrow where B-cell tumors occurred, increasing the amount of drug reaching the tumors compared with other methods, and prolonging survival.

Researchers have developed a new technique that enlists T cells to ferry chemotherapy drugs into tumors and that improves the efficiency of drug delivery.

Cancer cells can elude chemotherapy by hiding out in lymph nodes and other protected locations. Even if a small amount of drug makes it to these refuges, it may not permeate the tissue to reach the tumor cells inside.

Researchers have tried to overcome these problems by having nanoparticles transport chemotherapy drugs, but not all tumors have the leaky blood vessels that enable the particles to leave the bloodstream and disperse into the tumor.

Another approach uses immune cells as carriers, relying on T cells' tendency to home in on lymph nodes and the ability of T cells and macrophages to infiltrate tumors. For instance, researchers have inserted liposomes containing doxorubicin into macrophages, which then transported the liposomes into tumors in mice; the macrophage-delivered drug slowed the tumors' growth. A limitation of this approach, however, is that the drug has to exit the transporting cell to do any good.

To increase the amount of drug reaching tumor cells, Darrell Irvine, PhD, of the Massachusetts Institute of Technology in Cambridge, and colleagues devised a technique they call cell backpacking (Sci Transl Med 2015;7:291ra4). The backpacks are lipid nanocapsules loaded with SN-38, a version of irinotecan (Camptosar; Pfizer). On its own, SN-38 is a poor cancer drug because it's insoluble and doesn't readily enter tumors. The researchers reasoned that they could improve the drug's performance by using T cells to carry it to tumors.

Irvine and colleagues attached the backpacks to T cells and infused them into mice that had a rodent version of Burkitt lymphoma. The researchers found that the T cells traveled to three of the main locations where B-cell tumors form in this cancer: the lymph nodes, spleen, and bone marrow. Once they are in the animals' bodies, the SN-38–loaded capsules slowly break down and the drug diffuses out. Irvine and colleagues determined that the T cells delivered 63 times more SN-38 to tumor-bearing lymph nodes than injections of nanocapsules that contained the drug but weren't attached to T cells.

That increase made a difference for the mice. The overall tumor burden was 60 times lower in the animals that received the T cells loaded with SN-38 than in animals that received the drug alone. In addition, animals that received the altered T cells survived for 35 days, compared with control animals that lived just 24 days. “You get a tremendous increase in potency” with the cell backpacking method, says Irvine.

“I think what they've presented is promising,” says Susan Clare, MD, PhD, of the Northwestern University Feinberg School of Medicine in Chicago, IL. The higher pressure inside tumors can keep drugs out, but T cells are able to enter, she says. Clare adds that the technique might work for other cancers, including breast cancer.

The researchers didn't use antigen-specific T cells, but those cells might be able to home in on tumors in particular organs, Irvine says. He and his colleagues are looking into forming a company that would further develop the backpacking approach and potentially launch clinical trials.

For more news on cancer research, visit Cancer Discovery online at http://CDnews.aacrjournals.org.

©2015 American Association for Cancer Research.
2015