Adenovirus/PSA vaccine shows success in early trial

Key Points

Orlando, FL-A phase I trial shows that an adenovirus/ PSA vaccine is safe and can induce anti-PSA antibody and T cell responses in a significant number of men with stage D2 or D3 prostate cancer, researchers from the University of Iowa, Iowa City, reported at the AUA annual meeting.

Immune responses to PSA were measured in 40% of 32 patients in the trial, while anti-PSA antibodies were produced in 42%, and anti-PSA T cell responses were found in 71%.

The results were sufficiently encouraging that a phase II trial of the vaccine has already begun, said first author David M. Lubaroff, PhD, professor of urology and microbiology.

Point of attack

The adenovirus/PSA vaccine works by inducing immune responses to PSA on prostate cancer cells. When injected into patients, the virus enters cells at the injection site. Those cells, in turn, produce and secrete the PSA protein.

The protein-with the adenovirus likely acting as an adjuvant, Dr. Lubaroff said-is taken up by local antigen-presenting cells. These cells migrate to regional lymph nodes, where they induce anti-PSA T cells that exit the nodes and attack PSA-secreting tumor cells.

"Prostate cancer vaccines, including our adenovirus/PSA vaccine, are designed to induce strong immune responses to prostate cancer-associated antigens that result in the destruction of tumors," Dr. Lubaroff said. "All of us in this area of research have chosen what we believe to be the optimal vaccine and target antigen."

Patients in the trial were treated with a single subcutaneous injection at one of three dose levels (106, 107, or 108 plaque-forming units/mL). Some received the virus suspended in an aqueous solution, while others received it suspended in a Gelfoam matrix.

All patients returned for physical and clinical chemistry follow-up at 14 and 21 days, and at 2, 4, 8, and 12 months after injection.

Median survival in the trial was 18 months, with one patient surviving almost 6 years (range, 2.5 to 71 months).

Clear path to phase II

The investigators deemed the vaccine safe at all doses, with no difference found when it was administered in the aqueous solution or the Gelfoam matrix.

There were no vaccine-related adverse events. The most common adverse event was localized erythema/ecchymoses, which was found in nine patients.

PSA doubling time was increased in almost half (48%) of patients. A full 57% of men lived longer than would have been expected by the Halabi nomogram.

The vaccine's phase II trial will treat two populations of prostate cancer patients: those with newly recurrent disease and those with hormone-refractory cancer. Patients in the new trial will also receive three injections (a priming and two boosters, each 30 days apart), rather than one. The researchers also plan to enroll more patients in the phase II trial to help determine the vaccine's clinical efficacy.