Addition of a therapeutic cancer vaccine to standard chemotherapy has shown promise in a phase II trial of patients with metastatic colorectal cancer, according to an article in the August 1 issue of Clinical Cancer Research.

The vaccine, modified vaccinia Ankara-encoding 5T4, was designed to stimulate an immune response by patients: The vaccine used an attenuated live vaccinia virus to deliver the gene for 5T4, a protein found in many colorectal cancers.

When used in conjunction with standard chemotherapy, 6 of the 17 patients had a complete or partial response following independent expert review.

"The idea is that the modified virus enters cells, produces the tumor protein and stimulates the immune system," said lead study author Richard Harrop, PhD, vice president of clinical immunology at Oxford BioMedica. "To give a vaccine alongside chemotherapy might seem counterintuitive, since chemotherapy can weaken the immune system, but our study shows that TroVax could be complementary to standard chemotherapy, enhancing the immune response to tumors."

The tumor antigen called 5T4, a protein embedded within the cell membrane, is rarely found in normal tissues but is produced at high levels by a wide range of cancers including colorectal, renal, gastric and ovarian tumors. The production of 5T4 has been associated with cancer metastasis and poor prognosis for patients.

"Typically, the immune system doesn't pay attention to this molecule, so by producing 5T4 artificially in combination with the ‘danger signals' associated with a viral infection, we are demanding that the immune system take notice," Harrop said. "TroVax causes cells at the injection site to produce 5T4 in a way which agitates the immune system into producing antibodies and killer T cells. It is hoped that these two components of the immune system then migrate to tumors and kill them without harming any normal tissues."

Harrop and colleagues administered the vaccine to 17 patients with metastatic colorectal cancer just before, during and after treatment with the chemotherapy regimen FOLFOX (5-fluorouracil, folinic acid and oxaliplatin).

Through the course of the study, researchers monitored the patients for an immune response to 5T4. Of the 17 patients who received the complete course of vaccinations (six injections), 11 mounted strong immune responses to the 5T4 tumor protein. Of these 11 patients, six exhibited significant shrinkage of their tumors and one patient no longer had any detectable tumor.

Researchers noted no complications stemming from vaccination or any other evidence that would call into question the safety of the vaccine.

Although the study was not designed to prove that patients survived longer than would normally be expected, the researchers noted that, on average, overall median survival was 68 weeks in all 17 vaccinated patients and 118 weeks in the 11 patients who received all six vaccinations.

According to Harrop, the researchers are currently testing the vaccine in a phase III trial in renal cancer patients in the U.S. and Europe; Sanofi-Aventis is planning a phase III study in colorectal cancer.