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San Diego’s scientists have long been in the world’s top tier in unraveling the mysteries of cancer. Anyone even casually acquainted with the field can cite examples from UCSD, The Scripps Research Institute, the Salk Institute and biotechnology companies, such as Idec Pharmaceuticals.

But for cancer patients, it is a less positive story. San Diego has not been noted for its speed in transferring this top-ranked research from the lab to the patients’ bedside. Often, cancer patients have left San Diego to receive their care at such world-renowned institutions as the Fred Hutchinson Cancer Research Center in Seattle or Memorial Sloan-Kettering Cancer Center in New York City.

So while the discoveries and Nobel prizes pile up, cancer patients might be excused for wondering why San Diego’s oncologists can’t offer cancer treatment as good as its research.

Those days may be drawing to a close. San Diego’s academic scientists and oncologists are working together more closely than ever before to make these discoveries count in saving lives. This includes cancer vaccines to help the patient’s own immune system defeat the cancer and drugs that jam cancer’s genetic machinery, either by literally tying its DNA in knots or by blocking genes involved in cancer.

This change has evolved quietly at local biotechnology companies—the Sidney Kimmel Cancer Center, the John and Rebecca Moores UCSD Cancer Center, the Scripps Cancer Center, the Burnham Institute and other cancer programs throughout San Diego.

Two examples merit special attention:

• The Sidney Kimmel Cancer Center, which opened in 1990 as the San Diego Regional Cancer Center, has grown in the 12 ensuing years into a creative bridge between science and therapy. The center conducts basic research, performs clinical trials and has spun off 10 biotechnology companies.
  
  
• Cancer research and treatment is being invigorated from the field of bioengineering, where biology intersects with engineering and physics. One especially promising discovery — microscopic machines that can home in on cancer cells of various types for diagnostic or therapeutic purposes — came from a collaboration between Sangeeta Bhatia, a UCSD biomedical engineer, and the laboratory of Erkki Ruoslahti, a biologist at the Burnham Institute, also in La Jolla.

A long road remains, but the trend is becoming clear. Someday, cancer patients from across the country will make the pilgrimages to San Diego to find the best treatments.

It began At Busalacchi’s

Allan Goodman encountered San Diego’s lack of top-tier cancer treatment in the most painful way imaginable when his son Bob fell ill with leukemia. Goodman, a doctor but not an oncologist, searched the country for the best treatment, taking Bob to the Fred Hutchinson Cancer Center, to the Stanford Medical Center and the Jonsson Comprehensive Cancer Center in Los Angeles.

The best was not good enough: Bob died in 1989.

While Goodman was undergoing his personal tragedy, two leading cancer clinicians in San Diego, Ivor Royston and Thomas Shiftan, were frustrated with the limitations of cancer therapy in this city.

Royston already had won fame as the co-founder of Hybritech Inc. with Howard Birndorf, thus launching San Diego’s biotechnology industry. When Eli Lilly bought Hybritech in 1986, Royston helped found another biotech, Idec Pharmaceuticals, which began developing new cancer treatments.

All the while, Royston held a faculty position at the UCSD School of Medicine, where he headed an immunology lab supported with grants from the National Institutes of Health. But Royston felt stymied by what he called a disconnect at UCSD between research and treatment. The university’s top-notch research was not getting to patients fast enough, Royston says.

The situation today is quite different, Royston emphasizes, because UCSD has greatly strengthened its cancer center’s ties to both researchers and clinicians. The university is about to build an expanded center at a cost of $100 million, provided by John and Rebecca Moores and other donors. It is scheduled for completion in the fall of 2004.

“They had the basic science on the La Jolla campus, they had the clinical science Downtown (at UCSD Medical Center), and it was not well-integrated,” Royston says. “There was not an emphasis on translational research, moving new therapies from the laboratory to the clinic. I felt there was a need for a center that specialized in that.”

Royston talked his frustration over with Shiftan, an oncologist and a personal friend. Shiftan then told him of Goodman’s experience. Royston, Goodman and Shiftan got together in 1990 for lunch at Busalacchi’s Ristorante in Hillcrest. Over their meal, the three decided to found a new cancer center dedicated to hastening the move from the laboratory to the patient’s bedside.

Bootstrapping

Royston’s entrepreneurial skills were put to the test in founding the center, much as they were when founding Hybritech. The center needed four things: cash, researchers, ties to clinical oncologists and federal approval for the venture.

“You have to say, are you willing to take a risk?” Royston says. “Few people are. I said, ‘I have a bunch of grants from the government. Let’s find somebody who will lease us some space.’”

Usually, cancer centers are founded on grants from philanthropists, and then scientists are recruited. The opposite took place at the San Diego Regional Cancer Center.

Royston, Shiftan and Goodman took out personal lines of credit and went to see Chris McKellar, a prominent real estate developer. McKellar offered them the best deal imaginable: he would renovate vacant space on Torrey Pines Mesa into laboratories suitable for the cancer center. McKellar would then lease them the space with no money down.

Sidney Green, the retired administrator for the La Jolla Cancer Research Foundation (now the Burnham Institute), agreed to run the center for a while. Royston then notified UCSD and the NIH of his intention to switch his grants to the new center. After the NIH approval, the San Diego Regional Cancer Center was officially formed in June of 1990.

The effort was controversial. Naturally, UCSD administrators weren’t happy with Royston’s suggestion that their cancer program was flawed. Gerard Burrow, then the acting director of the UCSD Cancer Center, was quoted in the Dec. 10, 1990, issue of The Scientist as saying the new cancer center was not needed.

Royston replied in the article that he intended to coordinate with existing local cancer centers. And Green said he was called crazy when he founded the La Jolla Cancer Research Foundation in 1976 with a mere $250,000.

Big Breaks

Royston began recruiting more scientists, including one from Idec Pharmaceuticals who wanted to return to academic research. The two biggest breaks were teaming up with Sharp HealthCare and getting major funding from clothing magnate Sidney Kimmel. Others soon followed.

The center became a Sharp affiliate in 1994. Sharp agreed to help fund the center, and in return, the center agreed to carry out its clinical work at Sharp hospitals. This collaboration produced the first gene therapy treatment in San Diego.

Kimmel’s $5 million gift in 1996 changed the center’s name from the San Diego Regional Cancer Center to the Sidney Kimmel Cancer Center. In 2000, Kimmel bought the center $4 million worth of adjacent land on which to build its own campus. Earlier this year Kimmel kicked in another $12 million, bringing his total donations to $21 million.

In 1999, the center got a $4.7 million grant from the NIH for research on prostate cancer, working with researchers at UCSD, the San Diego Veterans Administration hospital and the Ludwig Institute for Cancer Research.

Last year prominent cancer researcher Albert Deisseroth became the center’s president and chief executive officer. An oncologist at Yale University School of Medicine who also conducted research, Deisseroth had the expertise required to work in both worlds. Royston, who had been running the center, left to work full time at Forward Ventures, a local venture capital firm he co-founded.

Today, the cancer center is readying a clinical trial of a molecule called icon to treat melanoma, a deadly form of cancer. The molecule, discovered at Yale, targets the blood vessels in tumors so the immune system can destroy them. It does not appear to harm healthy tissues.

Another measure of the cancer center’s influence is that it has given rise to 10 biotech startups. One, Favrille, is testing a therapy made from the cancer tissues of patients with B-cell non-Hodgkin’s lymphoma. The therapeutic vaccine’s goal is to stimulate the patient’s immune system into attacking and destroying the cancer cells.

For now, the startups operate out of the Sidney Kimmel Cancer Center. When any grow large enough, they’ll move out. So the center has added the role of incubator to its mediator function.

Fantastic Voyage

UCSD researcher Sangeeta Bhatia teamed up with the Burnham Institute’s Ruoslahti for another kind of cross-platform effort, bridging the animate and inanimate worlds with a hybrid device that can detect cancer and potentially deliver therapeutic drugs to kill cancer.

Bhatia, then an associate professor of bioengineering, thought that tiny semiconductor crystals called quantum dots could be the basis for microscopic machines that could attack cancer. They would swarm to diseased tissues and either identify the disease site or treat it directly, curing from inside out.

Ruoslahti knew of a good delivery vehicle — peptides, or small protein molecules, called homing peptides, developed at the Burnham Institute. These can be designed to go to specific locations in the body, such as the vascular tissue inside the lung, skin, pancreas or brain. The concept is like the 1967 sci-fi movie, “Fantastic Voyage,” sans Raquel Welch.

The impetus was a federal challenge to engineering researchers to find a way to treat cancer. “The National Cancer Institute was frustrated with the fact that there are a lot of technological advances going on in engineering, and that cancer therapy is still basically chemotherapy and radiation,” Bhatia says. “Their thinking was, If we set up a wish list for the engineering community, maybe that will catalyze some new solutions. They came up with a bunch of requests for proposals for ‘crazy ideas.’ We want something that will circulate in the body and detect cancer, it will relay the fact to the doctor, it will then treat the cancer, and it will tell the doctor how it went.”

Bhatia decided that starting simply was the best way to approach such a monumental challenge. She developed quantum dots that emitted certain colors when exposed to light. Ruoslahti devised homing peptides to seek out a specific cancer, in this case breast cancer.

The experiment, carried out in mice, was a success: the peptide-bound quantum dots attached themselves to breast cancer tissue. The results were published in September in the Proceedings of the National Academy of Sciences. (However, this won’t immediately lead to a human diagnostic, as the mice had to be killed.)

Better Than Machines?

With this proof of principle validated, Bhatia is looking to design more sophisticated micro-machines that can perform advanced diagnostic and therapeutic functions. For example, it may be possible to make quantum dots that shine when exposed to infrared light, which penetrates skin to a certain extent. This would result in a painless cancer test.

Moreover, the success of homing peptides could make cancer drugs more versatile, Bhatia says. A new class of medications, such as Idec’s Zevalin, use the missile and warhead strategy. They use monoclonal antibodies to home in on cellular targets, getting close enough to deliver a deadly payload from radiation or poison. Unlike traditional radiation or chemotherapy, monoclonal-delivered therapy is very precise at killing just the targeted cells, leaving other tissue unharmed.

Idec’s first monoclonal, Rituxan, was a major breakthrough: the first treatment of its kind for cancer. Even though most of Rituxan’s revenue goes to Idec’s partner, Genentech, Idec’s share of the take made it one of the few profitable biotech companies. Idec’s market capitalization today is more than $6 billion, and Idec is developing other drugs to keep its pipeline full.

However, Bhatia says monoclonal antibodies have flaws as molecular missiles. They are large protein molecules built from the same amino acid building blocks that make up the homing peptides. This means monoclonals have a tough time getting into parts of the body that homing peptides can easily reach.

In addition, Ruoslahti’s technology is easier to adjust to a target than monoclonal antibodies, and unlike monoclonals, you don’t have to know what precise part of the cell it’s attaching to.

“It’s kind of a brute-force way ... but once you have the recognition sequence, you just use it,” Bhatia says. “We can make tons of them, we can make them on a synthesizer. Dr. Ruoslahti has other peptides that make a cell internalize the particle. You can just keep adding functionality. You have one that finds the cancer, another peptide that makes it be internalized, another one that carries a drug.” Easy to make, easily able to go through the body and capable of precision targeting, homing peptides look like ideal missiles for cancer treatment.

Bhatia now is trying to develop micro-machines that would work by “positive feedback.” That is, once the particles encountered a target, they would signal for more particles to go to the site. This would result in large concentrations of any drug attached to the particles.

An Idea Grows Up

As the collaboration with Bhatia indicates, the Burnham Institute has come a long way from Sidney Green’s crazy idea in 1976. In October, Ruoslahti was elected to the Institute of Medicine of the National Academy of Sciences. Also last month, the institute recruited Evan Snyder, a prominent stem cell biologist, who will arrive in December.

“There are quite a few things to be proud of and optimistic about” in San Diego cancer research, says John C. Reed, the institute’s scientific director.

Reed arrived at the institute 10 years ago, bringing with him expertise on a phenomenon called apoptosis, or programmed cell death. It’s a major focus of cancer research, because cells that are as badly damaged as cancer cells should destroy themselves by apoptosis. But mutations in genes have shut down this process.

While Royston preferred to mix it up with academic research and clinical treatment, Reed came to the institute for the opposite reason: he wanted to focus on pure research.

“I was at an Ivy League medical school and was being diverted in 100 different directions with all kinds of teaching responsibility, committees, hospital work,” Reed says.

But Reed also wanted easy access to biotech companies that might be interested in his work. Reed had come up with an idea for a drug that would cause apoptosis in cancer cells. But pharmaceutical companies thought it was in too early a stage.

“I really became convinced we were going to have to start a company if we wanted to see these new therapies come to fruition,” Reed says. “I heard in San Diego there was a well-trodden path for nonprofit institutions hooking up with venture capitalists to do that sort of thing.”

In 1994, Reed solved his dilemma by co-founding Idun Pharmaceuticals to commercialize apoptosis therapies.

Work To Be Done

Reed concedes that San Diego still lacks the reputation of being a top-ranked center for cancer treatment. As evidence, Reed notes a recent U.S. News & World Report issue ranking the country’s top cancer treatment centers. The article listed UCSD, the only federally recognized cancer center, as number 42 in a list of the top 50 centers. Beating UCSD were such traditional favorites as the University of Texas M.D. Anderson Cancer Center in Houston, the Johns Hopkins Hospital in Baltimore and the Dana-Farber Cancer Institute in Boston.

“Certainly, those institutions have a long history of working with investigators who have been very active with organizing clinical trials to put experimental agents into patients,” Reed says. “There is still a lot of work to be done. There’s a long way to go, but things are happening.”