A therapeutic cancer vaccine has shown effectiveness when given alongside chemotherapy to patients with metastatic colorectal cancer in a phase II trial, according to researchers at Oxford BioMedica (UK) Ltd.
The study found that six of the 17 metastatic colorectal cancer patients in the study showed tumor shrinkage, classified as complete or partial responses following independent expert review.
The study, reported in the August 1 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research, was designed to demonstrate the safety and immunogenicity of the vaccine, called modified vaccinia Ankara-encoding 5T4 (TroVax), when used alongside standard chemotherapy. The research was funded by Oxford BioMedica which is developing the vaccine in partnership with Sanofi-Aventis.
Unlike preventative vaccines, such as the human papillomavirus vaccine to prevent cervical cancer, TroVax is a therapeutic vaccine, designed to stimulate the immune systems of patients who already have cancer. The vaccine consists of an attenuated (non-disease causing) version of the vaccinia virus modified to deliver the gene for 5T4, a protein found in many tumors.
“The idea is that the modified virus enters cells, produces the tumor protein and stimulates the immune system,” said lead study author Richard Harrop, Ph.D., 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 target of this immuno-therapy approach is a tumor antigen called 5T4, a protein embedded within the membrane of cancer cells. The protein is rarely found in normal tissues, but is produced at high levels by a wide range of human cancers, including colorectal, renal, gastric and ovarian. 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.”