Nanoparticles reprogram immune cells to fight cancer

Dr. Matthias Stephan has a bold vision. He imagines a future where patients with leukemia could be treated as early as the day they are diagnosed with cellular immunotherapy that’s available in their neighborhood clinic and is as simple to administer as today’s chemotherapy, but without the harsh side effects. The key to that scientific leap? Nanoparticles, tiny technology that’s able to carry tumor-targeting genes directly to immune cells still within the body and program them to destroy cancer. In a proof-of-principle study published Monday in Nature Nanotechnology, Stephan and other researchers at Fred Hutchinson Cancer Research Center showed that nanoparticle-programmed immune cells, known as T cells, can clear or slow the progression of leukemia in a preclinical model.

nanoparticles reprogram genes

“Our technology is the first that we know of to quickly program tumor-recognizing capabilities into T cells without extracting them for laboratory manipulation,” said Stephan, the study’s senior author. Although his method for programming T cells is still several steps away from the clinic, Stephan envisions a future in which biodegradable nanoparticles could transform cell-based immunotherapies — whether for cancer or infectious disease — into an easily administered, off-the-shelf treatment that’s available anywhere.

Stephan imagines that in the future, nanoparticle-based immunotherapy could be “something that is available right away and can hopefully out-compete chemotherapies. That’s my excitement.”


ImmunoTherapy Registers Success Against Brain Cancer

Using the immune system to beat cancer is quickly becoming a promising new strategy for battling tumors. But most of the success so far has been with blood cancers like lymphomas and leukemias. Immunotherapy, as it’s called, has yet to prove itself with solid tumors like breast, prostate, lung, colon and brain cancers.But in a report published in the New England Journal of Medicine, researchers led by Dr. Behnam Badie from the City of Hope Beckman Research Institute and Medical Center say that the same immune-based therapy that is successful against blood cancers also helped a patient with advanced brain cancer.

brain cancer

The 50-year-old man with glioblastoma, a particularly aggressive type of brain tumor, had already been treated with surgery, radiation and anti-tumor drug therapies. Despite these treatments, his cancer had returned and also spread to other parts of his brain and spinal cord. Badie and his team extracted immune cells from him, then engineered them to express proteins on their surface that would recognize and destroy glioblastoma tumor cells. After surgery to remove the bulk of the brain tumor, Badie and his colleagues directly injected the site with the modified immune cells (called chimeric antigen receptor T cells, or CAR T cells) six times, and the remaining part of this tumor stopped growing.

Other smaller growths in the brain continued to grow, however, so the patient received 10 more doses of the CAR T cells injected into the cavities in the brain, called the ventricles. This is the first time that immune cells have been injected into these brain regions, because introducing anything into the ventricles can cause dangerous and possibly deadly inflammation. The man did not develop such serious complications, however, and after about four months, these tumors too started to shrink. By six months, almost all had disappeared.

If the patient had not received the CAR T therapy, he likely would only have survived a few weeks after his cancer recurred, says Badie. But after being treated with the immune therapy, his cancer did not grow or recur for nearly eight months. “If we can do the same for other patients, that would be an amazing accomplishment that many decades of work and research on glioblastoma have never done,” says Badie, whose own father passed away a decade ago from glioblastoma.


New Immunotherapy Destroys Almost All Types Of Blood Cancer

cancer in bloodExperimental, living T-cell* therapy shows promise for treating advanced disease, making immunotherapy a ‘pillar’ of cancer care. Fred Hutch’s Dr. Stan Riddell and colleagues are making significant strides in this exciting field, and continue to refine ways to use the human immune system to overcome cancer and other diseases.

Twenty-seven out of 29 patients (more than 93%) with an advanced blood cancer who received an experimental, “living immunotherapy as part of a clinical trial experienced sustained remissions, according to preliminary results of the ongoing study at Fred Hutchinson Cancer Research Center.

Some of the patients in the trial, which began in 2013, were originally not expected to survive for more than a few months because their disease had previously relapsed or was resistant to other treatments, said Dr. Stanley Riddell, an immunotherapy researcher and oncologist Fred Hutch. Today, there is no sign of disease.

He shared the results as part of an update on new adoptive T-cell therapy strategies for cancer at the annual meeting of the American Association for the Advancement of Science in Washington, D.C. Riddell, who has studied how to empower the immune system to effectively treat human disease for more than 25 years, said that progress now being made, underscored by these latest results, is finally making immunotherapya pillar of cancer therapy.” But, he cautioned, “Much like chemotherapy and radiotherapy, it’s not going to be a save-all.” Some patients may require other treatments. The trial is designed to test the safety of the latest iteration of an experimental immunotherapy in which a patient’s own T cells are reprogrammed to eliminate his or her cancer. The reprogramming involves genetically engineering the T cells with synthetic molecules called chimeric antigen receptors, or CARs, that enable them to target and destroy tumor cells bearing a particular target. Trial participants include patients with acute lymphoblastic leukemia, non-Hodgkin lymphoma and chronic lymphocytic leukemia.

* T cells are white blood cells that can detect foreign or abnormal cells, including cancerous ones, and initiate a process that targets those abnormal cells for attack. But even when triggered, the natural immune response to a tumor is often neither strong nor persistent enough to overcome cancer cells.


Nanoflowers Deliver Drugs To Cancer Cells

Biomedical engineering researchers have developed daisy-shaped, nanoscale structures that are made predominantly of anti-cancer drugs and are capable of introducing a “cocktail” of multiple drugs into cancer cells. The researchers are all part the joint biomedical engineering program at North Carolina State University and the University of North Carolina at Chapel Hill.
To make the “nanodaisies,” the researchers begin with a solution that contains a polymer called polyethylene glycol (PEG). The PEG forms long strands that have much shorter strands branching off to either side. Researchers directly link the anti-cancer drug camptothecin (CPT) onto the shorter strands and introduce the anti-cancer drug doxorubicin (Dox) into the solution. Once injected, the nanodaisies float through the bloodstream until they are absorbed by cancer cells. Once in a cancer cell, the drugs are released.

Early tests of the “nanodaisy” drug delivery technique show promise against a number of cancers
We found that this technique was much better than conventional drug-delivery techniques at inhibiting the growth of lung cancer tumors in mice,” says Dr. Zhen Gu, senior author of the paper. “And based on in vitro tests in nine different cell lines, the technique is also promising for use against leukemia, breast, prostate, liver, ovarian and brain cancers.”