By Mary Welch
ImmvaRx Inc., a company only a few months old, is readying for Phase I trials of its synthetic peptide vaccines for cancer, as well as adjuvants to enhance human and animal vaccines.
The Evanston, Ill., company's pipeline is based on research by James Radosevich, an associate professor in the department of otolaryngology at nearby Northwestern University. His work originally was licensed to Immtech International Inc., also of Evanston, a biopharmaceutical company run by Stephen Thompson that developed therapeutic products for cancer and microbial diseases.
"While Jim's technology complimented our cancer programs, Immtech's focus shifted to the development of new therapies for treating opportunistic infections, so we decided to help launch Jim and ImmvaRx by raising separate private funds," said Thompson, acting president and CEO of ImmvaRx.
In the early 1980s, Radosevich produced monoclonal antibodies as molecular probes to identify and distinguish the various types of human tumors found in the lungs. Radosevich and the Northwestern researchers concentrated on carcinomas receptive to chemotherapy, and used a monoclonal antibody to deliver chemotherapeutics directly to the tumor. Although the agents proved useful against some tumors, side effects limited their expanded use.
Radosevich's monoclonal antibody, MCA 44-3A6, reacted with adenocarcinoma tumors of the lungs, and was employed to identify the important tumor specific antigen. This antigen, later cloned by Radosevich and called Labyrinthin, provided the basis for ImmvaRx's peptide cancer vaccine.
"We're using a synthetically produced cocktail of immunogenetic peptides derived from a cloned tumor-associated gene as a cancer vaccine," said Thompson. "We think it's a practical, economical vaccine that can be easily administered. Plus, patients who are at high risk for adenocarcinomas, which include a large number of breast cancers and some lung and colon cancers, can be treated to prevent their initial onset of the diseases."
Tumor-Specific Marker Found
The Labyrinthin protein is present in hard tumors, marking them so the natural immune system can attack, Thompson said.
"You want your own immune system to recognize tumor cells and rev-up your defense system to get rid of them," he told BioWorld Today. "The first step is to find a marker that is specific to the tumor. This is Labyrinthin. The next step is to make antibodies to this marker."
Radosevich cloned the gene responsible for the expression of the antigen and isolated a clone which expressed Labyrinthin. He then sequenced that gene and engineered the expression of its protein coding region. The cloned gene appeared to act like its biologically derived antigen.
An antisense gene was transferred into a tumor cell line that usually expressed generous amounts of Labyrinthin. The antisense copies became bound to the intermediates of the sense gene in the protein production pathway, and interfered with expression.
"There seems to be a lot of new evidence that patients which produce antibodies to their own tumors have a better survival rate with a better quality of life," Thompson said. "But that means taking the tumor out, chopping it up and putting it back into the patients. You can't really do that. But if you could get a synthetic version, well then ..."
That is ImmvaRx's aim. The company believes that it can safely stimulate the immune system to specifically attack adenocarcinoma tumors by immunizing patients with synthetic peptides that define key immunoreactive sites with the Labyrinthin antigen.
ImmvaRx, for which Peninsula Laboratories Inc., of San Carlos, Calif., is producing the peptide vaccine, plans to start Phase I proof-of-concept trials with about 30 to 50 patients by year's end or early next year. "Using animal models hasn't been the same thing," said Thompson. "But there is evidence from autologous vaccines that the antibody produced by Labyrinthin is present and effective."
Adjuvant Also Under Development
Another part of the company's strategy is to maximize the efficiency of its vaccines as well as others. ImmvaRx has secured the worldwide exclusive rights to use rmCRP — a recombinant, modified, biologically active form of the prototypic acute phase reactant C-reactive protein CRP — as an adjuvant. RmCRP was developed by Immtech.
Studies have shown that rmCRP boosts the immune response in animals immunized with Labyrinthin peptides alone. It is a naturally occurring human protein, and therefore "friendly" to the immune system. "That is important because many cancer patients have depressed immune systems which require additional stimulation," Thompson said. ImmvaRx intends to develop rmCRP as an adjuvant for other vaccines such as those against strains of the influenza virus, HIV, hepatitis B and hepatitis C, tick-borne diseases and tuberculosis.
With plans to continue its work through a partnership, the company is raising funds to meet its initial goal of $3 million. "We're about one-third there," Thompson said. *