June 25, 2003

Moores UCSD Cancer Center Launches Human Trial for Prostate Cancer Vaccine

Researchers at the Rebecca and John Moores UCSD Cancer Center today launched a human trial of a new experimental vaccine a type of gene therapy for prostate cancer. The therapeutic vaccine is based upon technology developed at UCSD.

The vaccine is prepared using the patient's own B lymphocytes, a type of immune-system cell, obtained through a simple blood draw. In their natural setting, these cells produce antibodies against molecules they sense are foreign or abnormal. In the laboratory, researchers genetically program the B cells to induce an immune response specifically against telomerase, an enzyme present in most cancer types. The genetically programmed B cells are given back to the patient through an intravenous infusion about 24 hours after removing them.

Frederick E. Millard, M.D., administers vaccine to patient.

The first person to receive the vaccine is a 66-year-old man from University City. His prostate cancer was diagnosed in 1997. Since that time he has undergone various standard treatments without success, including surgery, which left him cancer free "for a few years," radiation therapy, and most recently hormone therapy which, he says, worked for about a year.

"This approach is novel in many ways, but one important distinguishing characteristic is that it does not use viral or retroviral vectors to introduce the altered gene," said the study's principal investigator Frederick E. Millard, M.D.

Theoretically, this should reduce the risk of side effects, says Millard, who is also medical director of the Cancer Center's Clinical Trials Office, and associate clinical professor of medicine with the UCSD School of Medicine.

This clinical trial is offered only at UCSD, according to Millard.

To be eligible for the study, men of any age must have been diagnosed with hormone refractory prostate cancer, meaning they have undergone hormone therapy that is no longer effective. For further information call the Moores UCSD Cancer Center Clinical Trials Office, 858-657-7020.

Science Behind the Clinical Trial

Maurizio Zanetti, M.D.

The technology, called transgenic lymphocyte immunization, was developed in the laboratory of the Cancer Center's Maurizio Zanetti, M.D., a cancer immunologist and professor of medicine with the UCSD School of Medicine. Earlier his laboratory demonstrated that telomerase could be a target in cancer patients, a finding that generated international headlines when published in the Proceedings of the National Academy of Sciences, a major scientific journal, in April 2000.

"In that paper we identified telomerase as the first target that could work in just about every type of cancer prostate, breast, colon, lung, melanoma and possibly others," Zanetti said of the discovery, on which UCSD holds a patent. "That finding brings us closer to the possibility of developing a universal cancer vaccine, which puts this work in a different category than anything else now being tested."

Since publication of that paper, the researchers have gone on to identify the key sequences of telomerase that stimulate the desired immune response, and have inserted that portion into the gene for an immunoglobulin. This gene is incubated with the patient's B cells. The gene makes its way into the B cell unassisted, according to Zanetti, who said this is a new observation.

"No technology is needed," he said. "We are merely observers of this phenomenon, which happens by a means we don't yet fully understand. The process takes just 60 minutes, is done with small quantities of DNA and is 100 percent reproducible. This is apparently a natural propensity of the lymphocytes to internalize and use the type of genes that we have prepared."

Because no facilitating molecule or procedures are needed to deliver the gene into the cell, and because the gene is in the form of non-viral DNA, the researchers say, there is less concern that this approach will create any unwanted or unanticipated side effects.

Another deliberate part of the design is the selection of B cells to do the work of genetic vaccination.

"The B lymphocytes are powerful machines for making antibodies. That is their role in life," said Zanetti. "It is estimated that the average B cell can produce 1,000 antibody molecules per second. That's potentially a lot of antigen being produced when a B lymphocyte is programmed for immunization."

In this case, the B cells are expected to churn out immunoglobulin studded with a piece of telomerase, which will trigger an immune response against the cancer cells.

While it is early in the clinical testing of this approach and researchers aren't making any promises, they are optimistic about its potential, and say the beauty of this system lies in its simplicity.

"We have developed a system that we hope has resolved many of the problems experienced so far in developing vaccines," said Zanetti. "We use a machinery that exists and works optimally in nature. We don't have to manipulate the cells, which saves time and allows us to return a cell to the patient that is almost identical to what we received. And because the cell, like a tiny manufacturing plant within the body, generates elements of the vaccine, these are supplied continuously for some time."

The Rebecca and John Moores UCSD Cancer Center is one of just 39 centers in the United States to hold a National Cancer Institute (NCI) designation as a Comprehensive Cancer Center. As such, it ranks among the top centers in the nation conducting basic and clinical cancer research, providing advanced patient care and serving the community through outreach and education programs.

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