Two Cancer Researchers Among the 100 "Most Influential People in World"

Janis C. Kelly

May 27, 2010

May 27, 2010 — Two white-coated cancer researchers are among the luminaries picked for TIME magazine's 2010 list of the 100 most influential people in the world.

Larry Kwak, MD, PhD, and Doug Schwartzentruber, MD, FACS, join Sarah Palin, James Cameron, Steve Jobs, and Lady Gaga on this year's "influentials" list.

Both were included in the list because of their work in developing vaccines against cancer — Dr. Kwak for the BiovaxID personalized vaccine against follicular lymphoma, and Dr. Schwartzentruber for the development of a vaccine against metastatic melanoma.

Successful phase 3 trials with both vaccines were reported at last year's annual meeting of the American Society of Clinical Oncology (ASCO), as reported at the time by Medscape Oncology.

Lifetime in Cancer Vaccine Research

Dr. Larry Kwak

Dr. Kwak, who is professor and chair of the Department of Lymphoma and Myeloma at the University of Texas M.D. Anderson Cancer Center in Houston, was recognized for his 20-year commitment to the science of cancer vaccines, particularly for his role in developing a personalized therapy for follicular lymphoma.

Phase 3 data for the BiovaxID patient-specific vaccine for follicular lymphoma patients reported at the 2009 ASCO annual meeting showed a significant improvement in disease-free survival, as reported by Medscape Oncology.

Dr. Kwak pioneered the use of a patient-specific lymphoma vaccine and was the principal investigator for the BiovaxID clinical trials. The crucial component of the vaccine is a receptor protein extracted from the patient's malignant B cell lymphocytes, which is then combined with a delivery agent and an adjuvant growth factor and injected back into the patient.

"With lymphoma, you can get patients to a minimal disease state with chemotherapy and then bring in the vaccine to mop up remaining cancer cells. That's the strategy, and it should work for other cancers," said Dr. Kwak, who invented the vaccine while at the National Cancer Institute (NCI).

The phase 3 trial enrolled 234 follicular lymphoma patients. After chemotherapy, the 117 who went into complete remission for at least 6 months then received either the vaccine or a placebo. Median time to relapse was 44.2 months for the vaccinated patients and 30.6 months for the placebo-treated patients. Dr. Kwak said that some of these patients have remained in remission for several years.

Dr. Kwak, who described himself as "very surprised and flattered" at being included in the TIME 100, told Medscape Oncology that his interest in cancer immunotherapy dates back to high school.

"I grew up in Lawrence, Kansas, which is the home of the University of Kansas. Being near a university gave me valuable cultural opportunities, and as a high school student I took advanced courses at the university. One of these opportunities was an exposure to medical research. My mentor in high school introduced me to the idea that one could harness the immune system to fight cancer. That idea fascinated me, and I have been pursuing it since then. The advice I give my own 4 children is to find an occupation that you are passionate about, then your job does not feel like a burden," Dr. Kwak said.

After high school, Dr. Kwak blazed through BS, MD, and PhD degrees at Northwestern University, in Chicago, Illinois, in 7 years, and then headed west.

"I knew after graduating from high school that my passion was to have a career as both a physician and scientist. My vision was to make medical discoveries in a research laboratory and then to translate these discoveries to patients myself. Northwestern University offered me an accelerated program. I then completed a residency in internal medicine and a fellowship in medical oncology at Stanford University [in Palo Alto, California], which equipped me for a dual career as physician and scientist," Dr. Kwak said.

With a distinguished career at NCI and now at the M.D. Anderson Cancer Center, that is how things are working out. Medscape Oncology asked Dr. Kwak what kept him going through the long years required to bring BiovaxID from bench to clinic, and now nearly to bedside.

That has kept me focused and humbled at the same time.

"One of my patients once told me during a particularly difficult time that I am an instrument of God. That has kept me focused and humbled at the same time. You could say I feel it has been a calling," Dr. Kwak said.

The US Food and Drug Administration (FDA)'s recent approval of Dendreon's Provenge vaccine for certain forms of advanced prostate cancer sparked enthusiastic stories in the consumer press about vaccines to cure cancer, but Dr. Kwak is more reserved.

"I need to emphasize that we still have work to do, because this vaccine [for follicular lymphoma] is not yet available to patients on a large scale," he said. "This pivotal clinical trial has given us a "foot in the door," but the vaccine still needs to be approved by the FDA, and some additional clinical trials will probably be needed to verify these results."

The phase 3 trial also provided a boost to BiovaxID maker Biovest International, Inc., which announced, on April 19, a settlement with its largest creditor, paving the way for the company to file a Plan of Reorganization, emerge from chapter 11 bankruptcy, and proceed with the commercialization of BiovaxID.

"A former colleague once explained the 3 Ds of bringing a new therapeutic to market. We have completed the discovery and development phases of this vaccine, but what remains is the delivery to patients. It has a very exciting promise, but it's not yet reality, and that's still the work that needs to be done," said Dr. Kwak.

Reaching that translational milestone is not at the top of Dr. Kwak's priority list, however.

"My family is very important to me. Even ahead of my career, the personal accomplishment of investing in my family and raising the next generation would be at the top of the list. I am very involved in raising our 4 children, especially when they were younger, I coached some of their team sports activities and rarely missed their music events," Dr. Kwak said.

"Now that the children are older (3 boys aged 17, 19, and 23 years, and 1 girl aged 15), my wife and I love to travel internationally," he said.

Another Cancer Vaccine

Dr. Doug Schwartzentruber

For years, ASCO meetings have been littered with the debris of unsuccessful cancer vaccine trials. But last year saw not only a plenary session presentation for Dr. Kwak's vaccine for follicular lymphoma, but also a successful phase 3 study of a vaccine for metastatic melanoma, gp100.

This melanoma trial was headed by Dr. Schwartzentruber, medical director of Goshen Health System's Center for Cancer Care in Indiana. He began work on the clinical trial while still at the NCI, and continued as lead author and principal investigator after returning to his hometown of Goshen and accepting the medical director position.

The multi-institutional study reported at ASCO 2009 tested immunization with the gp100:209-217 (210M) peptide followed by high-dose interleukin (IL)-2, or IL-2 alone in patients with metastatic melanoma. The response rate improved to 22.1% with vaccine plus IL-2, compared with 9.7% with IL-2 alone (P = .0223). The researchers found that progression-free survival was 2.9 months with the vaccine plus IL-2 and was 1.6 months with IL-2 alone. Median survival was 17.6 months and 12.8 months, respectively.

"I first became interested in immunotherapy approaches to treating metastatic melanoma when I went to the surgery branch of the NCI for an immunotherapy fellowship," Dr. Schwartzentruber told Medscape Oncology. "My clinical research has always focused on metastatic melanoma. In the laboratory, I also pursued studies on the immune recognition of breast cancer. However, I never considered moving into other areas of cancer research."

Like Dr. Kwak, Dr. Schwartzentruber was surprised to be included in the TIME 100 list. "I keep thinking there are so many others more deserving; others who have accomplished so much," he said. "I certainly did not expect this, and I certainly do not deserve all the credit. There are so many individuals involved in the study, from the Goshen Center for Cancer Care for supporting the study to the doctors and research colleagues involved, to the patients who made the results possible."

The outcome of the phase 3 melanoma study was somewhat unexpected, even to the investigators.

"As a scientist designing a clinical trial, one must be prepared for any result. Seeing positive results from a trial that substantiated the smaller initial observation of a phase 2 study was a surprise," Dr. Schwartzentruber said.

Currently, the researchers are working on improving the vaccine before undertaking more clinical trials.

"Despite years of vaccine research, I believe that we are still in the infancy of its clinical applications," Dr. Schwartzentruber said. "Future steps involve making more potent vaccines; namely, identifying better adjuvants to increase the immunogenicity and efficacy of the vaccines. Because of the HLA restriction of peptide vaccines, developing vaccines for a broader repertoire of HLA types is also needed."

Dr. Schwartzentruber is an outdoorsman who enjoys snow and water skiing. "Occasionally, I do some fishing," he admitted. "Even the more mundane task of yard work is a good diversion from my professional duties."

Dr. Kwak and Dr. Schwartzentruber have disclosed no relevant financial relationships.

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