By Cathy Dunn

Mention the word “vaccination” and most of us think of the old standbys: smallpox‚ measles‚ polio‚ diphtheria‚ chicken pox‚ and influenza. These time–tested immunizations have saved countless lives. Now experimental cancer vaccines may save many more.

Bruce Cameron is living proof of the innovative therapy’s effectiveness. The energetic 70–year–old from Santa Rosa‚ California‚ leads a healthy‚ productive life thanks to a vaccine that has kept his lymphoma in check for nearly 15 years.

“I was diagnosed with non–Hodgkin’s lymphoma in 1987 and immediately began chemotherapy‚” says Cameron. “The powerful combination of drugs was too much for my system. I developed a high fever and had to be hospitalized.”
Despite complications‚ Cameron completed his six–month chemotherapy treatment course and continued to manage the family vineyards‚ a job he still holds today.

Chemotherapy shrank Cameron’s tumors but did not get rid of the disease. At his doctor’s suggestion‚ he enrolled in a groundbreaking clinical trial in 1988 under the direction of Ronald Levy‚ MD‚ chief of oncology at Stanford University School of Medicine‚ Stanford‚ California. Dr. Levy‚ a pioneer in cancer treatment‚ began lymphoma vaccine research in the early 1980s.

“Unlike other types of vaccines‚ which prevent illness‚ cancer vaccines are designed to halt recurrence in patients who already have the disease‚” Dr. Levy explains. “Vaccines must be custom made from a patient’s own cells. Lymphoma is ideal for this type of treatment because some forms of the disease grow slowly‚ allowing enough time for individual serum to be manufactured in the lab.”

The vaccine–making process is highly sophisticated and requires several steps. First‚ a patient’s tumor cells are removed through biopsy. Cancer–associated proteins are extracted from the cells and combined with a carrier protein called keyhole limpet hemocyanin (KLH). KLH‚ which is derived from sea snails‚ stimulates the immune response because the body recognizes it as an invader. When the tumor cell–KLH concoction is injected into the body as a vaccine‚ the immune system not only attacks KLH‚ but also recognizes its own cancerous cells and destroys them as well.

“The body’s immune system is not designed to attack its own cells‚ even if they are abnormal‚” says Dr. Levy. “One of our most difficult challenges is to find ways to effectively enlist the immune system’s help in recognizing and destroying cancer cells as if they were a virus or bacteria. Using a foreign substance like KLH to carry cell proteins is one of many techniques being tested.”

Dendritic Cells Learn New Tactics
No vaccines have yet received U.S. Food and Drug Administration (FDA) approval‚ but clinical trials using vaccine therapy to target a variety of cancers are being conducted nationwide. One successful program is under way at Baylor University Medical Center (BUMC) in Dallas‚ Texas‚ where dendritic cell vaccines are being used to treat patients with metastatic melanoma.

“Dendritic cells activate and regulate the body’s immune system‚” says Joseph W. Fay‚ MD‚ director of Immunologic Therapy for Cancer‚ Baylor Institute for Immunology Research.

“These cells constantly patrol the body‚ looking for trouble. In an immature form‚ they circulate in the blood and lie dormant in the tissues. When they sense the presence of a virus or bacteria‚ they mature rapidly and assume the role of commander‚ directing several types of immune cells—the ‘troops’—to destroy the enemy. This is precisely our goal in the treatment of cancer.

“Tumor vaccine treatment for melanoma is a good model for dendritic cell immunotherapy because we already know a lot about the proteins and peptides melanoma cells possess. These serve as targets for an immune attack‚” he adds.

Each customized vaccine is made of dendritic cells from a patient’s blood‚ tumor antigens‚ and a stimulant that causes dendritic cells to mature and become active. Patients receive injections every two weeks for two months. Those who respond well receive four booster shots.

Dallasite Gary Scott is one of the study’s success stories. For years‚ Scott and his doctors had been watching a suspicious mole on his upper back. When a bump started to grow under the mole‚ Scott knew it was time to take action. By the time he was diagnosed with melanoma and had undergone surgery‚ the disease had spread to his liver.

His surgeon at Baylor‚ Joseph Kuhn‚ MD‚ estimated he had about six months to live. When Scott heard the news‚ he had only one request.

“I asked Dr. Kuhn to keep me alive long enough to celebrate the birth of my grandchild‚” says 69–year–old Scott. That was more than two years ago. Today‚ he’s been cancer–free for more than 18 months and regularly visits his granddaughter‚ Karen‚ now a toddler.

Scott has now turned his attention to writing his memoirs. The most important chapter chronicles his successful battle against his devastating disease.

“Early results of our clinical trials have shown that dendritic vaccines can activate the immune system to attack a patient’s own cancer cells‚ resulting in durable remissions without side effects‚” Dr. Fay reports.

Buoyed by their early results with melanoma‚ researchers at BUMC‚ with support from the National Cancer Institute‚ are now developing clinical trials using more sophisticated dendritic cell vaccines against melanoma‚ prostate‚ and breast cancers.

Vaccine–Like Drugs Join the Fight
Other researchers are testing drugs that act like vaccines. Among those are OvaRex® (ovarian cancer)‚ Theratope® (breast and colon cancers)‚ and GVAX®.

“OvaRex‚ a monoclonal antibody directed toward CA–125 [an elevated substance in the blood of ovarian cancer patients]‚ mimics a cancer vaccine because it induces a series of immune system responses which appear to produce an antitumor effect‚” notes Jonathan S. Berek‚ MD‚ chief of the division of gynecology and gynecologic oncology at the David Geffen School of Medicine at UCLA‚ University of California‚ Los Angeles.

Theratope synthetically mimics breast cancer antigens and tricks the body into attacking wayward cells. Researchers hope to use this drug to trigger the appropriate immune responses that will control growth‚ prevent or delay spread of the disease‚ and increase survival odds.

GVAX is comprised of tumor cells that have been genetically modified to secrete granulocyte–macrophage colony stimulating factor (GM–CSF)‚ a hormone that plays a key role in stimulating the body’s immune response to vaccines. Originally developed to treat metastatic prostate cancer‚ GVAX is also being tested in melanoma‚ pancreatic‚ lung‚ and renal cancers.

“Growth factor hormones like GM–CSF‚ granulocyte colony stimulating factor (G–CSF)‚ and FLT3–L are crucial in dendritic cell vaccine development because they increase the number of immature dendritic cells in the bloodstream that can be used in manufacturing vaccines‚” says Dr. Fay. “These and other growth factor hormones mobilize the body’s dendritic cells and other immune cells like neutrophils‚ macrophage‚ and natural killer cells‚ which can then be directed against cancer.”

There are obstacles to overcome. For example‚ producing the vaccine is often a difficult and expensive process. Nonetheless‚ researchers predict a bright future for cancer vaccine development.

“I’d like to see cancer vaccines replace chemotherapy altogether‚” says Dr. Fay. “And I think someday that will happen.”

“In five years‚ I hope every patient with lymphoma has an opportunity to be vaccinated‚” Dr. Levy adds. “If we can accomplish that‚ we can improve both the quality and quantity of life.”

If these predictions come true‚ many other cancer patients‚ like Cameron and Scott‚ will have a chance to celebrate a new lease on life.