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Killing Cancer Through the Immune System (Part II)

Treating the Patient Instead of the Disease

By Michael Howerton    |   UCSF.edu | February 4, 2014

Killing Cancer Through the Immune System (Part II)

Lawrence Fong, MD, and Jera Lewis, a staff research associate in Fong's lab, pull cryopreserved patient samples stored in a liquid nitrogen tank to assess for immune responses. Photo by Susan Merrell

continued from "Killing Cancer Through the Immune System," Feb 4, 2014, UCSF.edu 

“For the longest time, people did not believe this was possible,” said Lawrence Fong, MD, associate professor of medicine at UCSF and one of the University’s lead investigators in the expanding use of immunotherapy.


Cell cultures containing growing tumor cell lines are stored in Fong's lab.Photo by Susan Merrell

Fong and Yafei Hou, MD, PhD, a specialist in the Fong Lab, discuss which treated patients they plan to assess for immune responses. Photo by Susan Merrell

“Now we can treat cancer by treating the patient instead of the disease,” he said. “That’s the biggest change. We can treat cancer without delivering chemotherapy or radiation to kill the cancer or performing surgery to get rid of the tumor.”

Researchers at UCSF and elsewhere have identified cell receptors, such as CTLA-4 and PD-1, which act as a brake on the immune system, limiting its response.

With the use of antibodies to inhibit these blockade receptors, allowing a more active and vigilant immune system, doctors have seen outstanding responses in patients with metastatic melanoma and lung cancer, both of which are almost always fatal with conventional treatments. Immunotherapy also has been successful in cancers of the bladder, prostate, kidney and bone marrow.

“This was a radical idea: that the body already possesses the ability to defeat cancer, and that medicine’s role was to find a way to allow the body to marshal the healing work it is naturally capable of,” Fong said. “We all believed it could work, but very few would have predicted the 180-degree change that we’ve seen over the last two years.”

Ever since James Allison, PhD, developed the first drug that increased survival for patients with metastatic melanoma while at UC Berkeley – an antibody against CTLA-4 called ipilimumab that was approved by the U.S. Food and Drug Administration in 2011 – it has been like a door has swung open.

In December, Allison – now chair of the University of Texas MD Anderson Cancer Center’s Immunology Department – won one of the 2014 Breakthrough Prize in Life Sciences for his groundbreaking discovery. Max Krummel, PhD, who co-developed ipilimumab while a graduate student in Allison's lab, is now a pathology professor at UCSF.

Indeed, the treatment has been a hot topic at recent cancer conferences and all top pharmaceutical companies are developing immunotherapy drug programs. Science magazine declared immunotherapy its top breakthrough of 2013.

Bluestone’s UCSF lab was the first to show that CTLA-4 can turn off the immune system’s T-cell attack when studying its application to organ transplants and autoimmune disease, a discovery that help paved the way for Allison’s application to cancer.

He pointed to the University’s continuing role in pushing the field ahead, including recent work in cell therapy, which uses stem cells taken from a patient, corrects the gene mutation that causes disease and returns the “gene-corrected” cells to the patient for therapy.

This work is part of UCSF’s commitment to precision medicine, which aims to harness the wealth of genomic, clinical and environmental data from patients to develop more effective and even preventive therapies for human diseases.

“It has been a sea change that has been transformational,” Bluestone said, “not only from the patient’s point of view, but also for our understanding of the relationship between cancer and the immune system and how to treat disease.”

 

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