A phase I trial has documented for the first time that a vaccine with a cancer-specific recombinant antigen has successfully induced a fully integrated immune response in humans, according to an article in the March issue of the Journal of Immunology.

In the current study, patients with non-small cell lung cancer received a vaccine of recombinant protein MAGE-3 and the immunological adjuvant AS02B. MAGE-3 is a member of a family of highly cancer-specific antigens found on a wide variety of tumors, and AS02B stimulates the immune response to the protein. Most of the antigen-specific cancer vaccines that are currently in early-phase clinical trials use peptides. In contrast, the trial cancer vaccine contained the full-length protein antigen, a design that matches that of most infectious disease vaccines routinely used today.

Previous cancer vaccines had been shown to induce vaccine-specific antibodies and CD8 T-cells. However, antibodies and CD8 cells represent only two parts of a complex overall immune response. Investigators in the current trial also documented that the majority of patients produced CD4 T-cells in response to the vaccine; those cells enhanced CD8 T-cell activity and, most importantly, acted to sustain the attack on the cancer antigen for longer periods of time. The team used a new method that allowed researchers to monitor all three major components of the response to the vaccine.

The patients in the study are now being followed to measure long-term clinical response to the vaccine and to assess whether vaccine booster shots are necessary to maintain their immunization.

“We have a mantra for cancer vaccine development,” said Dr. Lloyd J. Old, senior author on the paper. “‘You will not know how to vaccinate until you know how to immunize. And you will not know how to immunize until you know how to monitor.’ Being able to monitor the full set of immunological responses allows us to specifically test different antigens and vaccine component combinations, like the addition of AS02B, and identify therapeutic responses that are associated with immune responses.”

The necessity of immunological monitoring to enable rational vaccine development was echoed by Dr. Herbert Oettgen. “We should keep in mind that every modern vaccine developed for infectious diseases has gone through a rigorous progression of testing components and monitoring the immune responses to establish strong and sustained immunization in humans. And yet cancer vaccines have often been given to patients without having demonstrated that they illicit a strong immune response.”

Dr. Jill O’Donnell-Tormey noted that the new monitoring method has entered use in clinical trials in Australia, Belgium, Germany, Japan, Switzerland, the United Kingdom, and the USA. “The ability to monitor is really making a big difference to our work. We are now using a systematic, coordinated approach to vaccine development, by comparing the immunological responses produced by single vaccine variables being tested in parallel at each of our different sites. We believe that this approach will yield cancer vaccines with the greatest efficacy, and in a much shorter time than the conventional approach of trying variables sequentially with limited monitoring of responses.”