Early results of a trial to treat leukemia with WT1 DNA vaccine have shown robust vaccine-specific antibody responses in all vaccinated patients evaluated to date. Furthermore, T cell immune responses that included killer T cells were detected. Both antibody and T cell responses are strong signals of the potential of the DNA vaccine to treat leukemia.

Leukemia is a cancer of the bone marrow and blood that accounts for at least 300,000 new cases of cancer and 222,000 deaths worldwide each year. Wilms’ tumor gene 1 (WT1) is highly associated with these types of cancer. Preclinical data from mice showed strong induction of antigen-specific CD8+ T cells and the ability to kill human tumor cells expressing WT1. This study is the first to combine DNA vaccination with electroporation delivery of WT1 antigens. The goal was to stimulate high and durable levels of immune responses, particularly T cells, which are considered critical to improve clinical outcomes for this disease.

In this ongoing phase II trial, all participants initially received six doses of two DNA vaccines that are delivered at 4-week intervals. Patients who are vaccine responders may continue with booster vaccinations every 3 months out to 24 months. The trial is enrolling an additional 60 to 75 patients with acute myeloid leukemia (AML) or chronic myelogenous leukemia (CML) across the two arms as nonvaccinated controls for comparison.

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The primary endpoints are molecular response to BCR-ABL, a disease marker in CML patients, and time to disease progression in AML patients. The study is also monitoring WT1 transcript levels, immune responses to WT1 antigen, time to progression, overall survival, and, in the AML group, 2-year survival.

To date, 14 CML patients have been enrolled, while another 13 nonvaccinated CML patients have been enrolled to serve as a control group. The vaccine has been shown to be safe overall and well-tolerated. The CML vaccinated group had favorable safety and immunogenicity profiles; therefore, the trial is now open to enrollment for the AML clinical trial arm. The total target is 37 participants in each of the vaccinated and control groups.

“These preliminary data show strong vaccine-induced immune responses in vaccinated subjects in the CML arm. We are looking forward to enrolling and testing the vaccine’s impact in AML patients, who currently have limited treatment options and a low rate of progression-free survival,” said Christian Ottensmeier, MD, PhD, of the University of Southampton, United Kingdom. He presented the results at the DNA Vaccine 2012 Conference held December 5-7, 2012, in San Diego, California.