Project 4: Th17 T Cell-Inducing Vaccines for the Prevention of Ovarian Cancer Recurrence

In this research project, investigators in the Mayo Clinic Ovarian Cancer SPORE are assessing the ability of a dendritic cell-based vaccine to prevent ovarian cancer recurrence.

Most ovarian cancers express folate receptor alpha (FRA), a cell surface protein that facilitates uptake of folic acid (vitamin B-9). Ovarian cancer also mounts a weak immunological reaction to FRA, which is absent or inaccessible on normal cells in adults. This project involves boosting that immune response so that each person's immune system recognizes and eliminates cancer cells expressing FRA.

Previous trials of immunotherapy in ovarian cancer have had poor response rates and limited durable remissions.

A unique strategy

The current vaccine strategy is unique in several ways:

It induces a specific type of immunity, called Th17 immunity, that seems to prevent suppression of the immune system.
The vaccine is administered after initial surgery and neoadjuvant or adjuvant therapy, when the tumor burden is lowest and the chances of eradicating all remaining tumor cells is greatest.

The vaccine is generated from each person's healthy monocytes by differentiating them into antigen-presenting cells (dendritic cells), pulsing them with peptides (fragments) from FRA, and maturing them so that they induce a Th17 immune response. A previous phase 1 study showed that the vaccine was safe and induced a higher than expected rate of relapse-free survival in ovarian cancer in first remission.

Project aims

To build on our previous results, this project is:

Using animal models to study the immunological processes triggered by the vaccine that makes it so effective and elucidating what goes wrong when it fails to work.
Conducting a placebo-controlled randomized phase 2 clinical trial of the vaccine and assessing initial ovarian cancer diagnostic samples for potential biomarkers that predict a favorable outcome with the vaccine.
Assessing multiple facets of each person's immune response to the vaccine to determine whether any of these factors also correlate with clinical response.

Goals

We expect this project to provide a further test of a novel vaccine strategy and offer new insight into which people with ovarian cancer are most likely to benefit from the vaccine.