Vaccine induces anti-PSA antibody, T cell response in PCa patients

May 18, 2008

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, according to findings from a phase I trial conducted at the University of Iowa, Iowa City, and reported here yesterday.

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, according to findings from a phase I trial conducted at the University of Iowa, Iowa City, and reported here yesterday.

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%. Results were sufficiently encouraging that a phase II trial of the vaccine has already begun, says study co-author David M. Lubaroff, PhD, who worked on the research with Richard D. Williams, MD, and colleagues.

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, 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.

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; 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).

PSA doubling time was increased in 48% of patients, and 57% of men lived longer than would have been expected by the Halabi nomogram.

"Trials such as ours will help us understand whether vaccine immunotherapy can be used to treat recurrent prostate cancer," said Dr. Lubaroff. "Although it is difficult to make any definitive conclusions from phase I trials other than the presence or absence of toxicities, we were very much encouraged by the immunologic and clinical results of the study."