One challenge in vaccine development is finding effective methods to introduce antigens that will provide cellular or humoral immune responses that are not only strong, but long lasting. To this end, Immunovaccine, an early stage vaccine company, has developed a formulation to enhance various vaccines, including those for infectious diseases and cancer.

Technology: DepoVax is a formulation that uses oil to create a depot. The technology uses liposome solutions as antigen and adjuvant carriers. The solution is then lyophilized, and oil is used as a diluent to resuspend the dry vaccine before use. Liposomes bring those water-soluble molecules of antigens and adjuvants directly into the oil. The result is a continuous oil environment in which the antigen and adjuvant are suspended.

After injection, the oil attracts the immune system to the site of vaccination. The oily vaccine in the tissue is then completely surrounded by cells of the immune system. As the immune cells come to the site, they slowly (over a period of weeks) take up antigen and adjuvant in the vaccine. “It is the combination of prolonged exposure of the immune system to the vaccine and taking up the antigens and adjuvants slowly over time that makes the vaccine work so much better,” explains Marc Mansour, COO and chief science officer at Immunovaccine.

Application: The company is developing two cancer vaccines that leverage the DepoVax technology. The antigens are synthetic-peptide–based and supplied by a separate manufacturer, whereas the adjuvant is a proprietary product.

For one vaccine, a nine-month phase 1 US trial involving 23 patients with either breast, ovarian, or prostate cancer showed that DepoVax is safe to use. No serious adverse events or dose-limiting toxicities were associated with the vaccine. “In addition, we observed an immune activity. That was the validation of DepoVax in humans,” says Mansour.

During that trial the company started work on a second cancer vaccine, which is based on the survivin protein. “Cancer cells have a hard time getting rid of survivin because they need it to survive,” says Mansour. “So it is a good therapeutic target, and by putting it in DepoVax, we are making it more immunogenic. It’s a target that’s applicable to several cancer types, and we decided to conduct a clinical trial in ovarian cancer as the proof of concept indication.” In June, the US Food and Drug Administration (FDA) approved proceeding to clinical trials for phase 1 (to be conducted before the end of 2012) and phase 2.

Challenges: Moving cancer vaccines past phase 2 requires addressing several issues. First and foremost, says Mansour, is having the right target so that the immune system will be able to tackle the cancer. “We think survivin is the right target. Most of these antigens are very weakly immunogenic; they don’t generate a strong immune response unless you put them into an enhancement platform such as DepoVax.”

But that alone is not enough. “You have to use cancer vaccines properly. You cannot use the vaccine in the late stages of cancer — when it’s terminal or difficult for the immune system to exert a dramatic effect on a large tumor. Cancer vaccines fit in the earlier stages of cancer.” Immunovaccine is testing in newly diagnosed patients who will undergo surgery and chemotherapy. “After surgery and chemotherapy they will receive the vaccine therapy and be monitored for a year and a half. On average a year and a half is the period of time when this type of cancer will come back. We will vaccinate, training the immune system to fight cancer cells and delaying them from coming back — adding quality of life and extending it at the front end.”

According to Mansour, one misconception is that a cancer vaccine will eliminate a large established tumor, like chemotherapy does. “It’s a different concept. A cancer vaccine that doesn’t have the side effects of chemotherapy. It’s very targeted. [After a tumor is removed by conventional means], the vaccine uses your immune system to help prevent those cells from coming back. How you use it defines whether that approach will work.”

Future Capabilities: The survivin protein is applicable to 90% of ovarian cancer patients, so selecting a population based on that target is possible. Future cancer vaccines and others, possibly within the next five years, should become even more targeted toward smaller populations. “You are selecting not only a subgroup based on the target, but a subgroup of a subgroup based on their response to the target. And you can make the final group smaller and smaller. The goal is to find a target that is as broadly applicable as possible and then focus the personalized approach on the patient’s immune system.”

— Maribel Rios, Managing Editor