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to arouse the immune system against a particular tumor type. For example, the GVAX prostate cancer vaccine is comprised of a human prostate cancer cell line with characteristic antigens on its surface that spur an attack from immune system cells. The cells are treated so they can’t multiply in the body. In addition, the GVAX vaccines are all engineered to release an agent that stimulates the immune system, granulocyte-macrophage colony-stimulating factor (GM-CSF).
While GVAX is in the running as a possible part of combination therapies with Aduro’s LADD cells, the companion drugs that seem to raise the most excitement both at J&J and at Aduro are the checkpoint inhibitors such as Bristol-Myers Squibb’s ipilimumab (Yervoy). This class of drugs—a hot topic in cancer research these days—turn off a molecular switch that otherwise protects cancer cells from the immune system.
In theory, the checkpoint inhibitors could boost the long-term effect of the T-cells that become dedicated to attacking cancer cells after exposure to the antigens produced by Aduro’s Listeria strains, Isaacs says. Aduro plans to explore this combination in pancreatic cancer. Isaacs says he has had discussions with BMS as well as Merck and Roche, which are also developing checkpoint inhibitors.
Janssen Biotech may pursue the same tactic. “We feel that parallel studies could be done in prostate cancer,” says J&J’s Molina.
Aduro and other companies are benefiting from “a new Renaissance for immunotherapy,” says William Chambers, national vice president for extramural research at the American Cancer Society. Chambers says Aduro’s approach—creating bacteria that live inside of dendritic cells—is unusual. In a more common tactic, researchers have tested bacteria as tools to kill tumors directly. Bioengineered bacteria have been designed to enter tumor cells, where they stay alive and manufacture drug agents to injure those host cells from within.
The technology of Princeton, NJ-based Advaxis (Nasdaq: ADXS) may be most similar to Aduro’s. Advaxis, which also uses bioengineered Listeria monocytogenes bacteria as a means to target the immune system against tumors, is testing its treatments in cervical cancer and other indications. Advaxis has formed partnerships with two biotechnology companies in Asia: Biocon of India and Global BioPharma of Taiwan.
Aduro will now have the resources to fund its own array of clinical trials. Isaacs says its licensing deal with Janssen Biotech, and its $55 million in new financing, will support the company’s operations into 2016. To date, Aduro has raised a total of $84 million in equity financing.
While pancreatic cancer is Aduro’s lead indication for CRS-207, the company has also conducted a small initial study of the Listeria-based therapy, along with chemotherapy, in patients with mesothelioma. This tumor type also bears the antigen mesothelin. Aduro plans to follow up with a randomized trial comparing the CRS-207 regimen with chemotherapy alone, Isaacs says.
In May, Aduro also began an initial safety trial of a different member of its Listeria vaccine family, ADU-623, in patients with high-grade glioma, a form of brain cancer.
Aduro also has a third technology in its toolchest: a group of compounds called cyclic dinucleotides, or CDNs. These are modified versions of naturally occurring small molecules that jump-start the immune response. In preclinical studies, the company has been evaluating combination therapies that include CDNs and GVAX—nicknamed STINGVAX.