The Best Shot

by Alicia Di Rado

Oncologists at the USC/Norris Comprehensive Cancer Center have begun a clinical trial to evaluate a unique vaccine therapy in the treatment of metastatic colorectal cancer.

USC/Norris is one of several sites in the United States and Canada participating in the trial.


The multi-center trial is enrolling up to 90 patients with previously untreated metastatic colorectal cancer, according to Heinz-Josef Lenz, M.D., associate professor of medicine and director of USC/Norris' gastrointestinal oncology program. Lenz is recruiting 10 to 20 patients.


"The goal of the study is to determine if the vaccine, called ALVAC-CEA/B7.1, can activate the body's own immune system to eliminate cancer cells that may not be eliminated with the standard, first-line chemotherapy regimen," Lenz says. "We will be looking to see if the vaccine, combined with chemotherapy, allows a better outcome for patients than chemotherapy alone."


Typically, vaccines such as those for chicken pox or measles are designed to prevent diseases by priming the immune system for a possible attack. With therapeutic cancer vaccines, though, the goal is to "turn on" the immune system of people who already have the disease, to increase the power of current treatments such as chemotherapy.


While the immune system exists to respond to invaders, attack them and rid them from the body, it has a hard time recognizing cancer cells as targets because cancer cells arise from the body's own tissue.


The colon cancer vaccine under study consists of a form of live virus engineered to stoke the body's immune system in a specific way to battle cancer.


ALVAC is a variant of the canarypox virus; it produces a self-limiting infection that does not cause any harm or symptoms in humans.


This is how it works:
Most colorectal cancers overexpress a protein called carcinoembryonic antigen, or CEA. If the immune system could come to recognize CEA as a sign of something foreign or abnormal, it would then detect and attack cancer cells that have CEA on their surface.


That is where the vaccine comes in. The virus variant in the vaccine is engineered to cause infected cells in the body to temporarily display CEA, which signals the immune system to attack tumor cells with CEA on their surface.


In the clinical trial, patients are divided into three groups.


One group is vaccinated before starting standard chemotherapy and then receives a vaccine injection weekly during the chemotherapy regimen.


A second group receives that same treatment, as well as a tetanus shot, to see if that boosts immune response.


A third group receives standard chemotherapy, and those who respond to the chemotherapy have the option of receiving the vaccine at the end of the trial if they like.


Standard, first-line therapy for metastatic colorectal cancer involves combination chemotherapy with three agents: Camptosar (irinotecan or CPT-11), 5-fluorouracil and leucovorin.


The investigational vaccine and other ALVAC-based formulations have shown promise in early clinical studies of the vaccine as a single agent. Treatments generally were well-tolerated, and side effects associated with the vaccine included mild, local reactions.


The trials were conducted by the National Cancer Institute in collaboration with Therion Biologics of Cambridge, Mass. Aventis Pasteur Limited of Toronto, Canada is the study sponsor.


Lenz believes that in the future, such immunotherapies may be combined with genetically tailored chemotherapy regimens to create treatments that have the greatest chance of success for each patient.

For information about the colorectal cancer vaccine clinical trial, contact the USC/Norris Clinical Investigation Support Office at (323) 865-0451.