Vaccinating Advanced Prostate Cancer Patients With PSCA & PSA Peptide-loaded Dendritic Cells Induces DTH Responses That Correlate With Superior Overal

Prostate cancer stem cell antigen (PSCA) and PSA are over-expressed in most prostate cancers (CaP). Dr. Thomas-Kaskel and colleagues from Freiburg, Germany report on a dendritic cell (DC) vaccine using PSCA and PSA in the early view version of the International Journal of Cancer.

Peripheral blood mononuclear cells were cultured in the laboratory and transformed into DCs using cytokines. Several PSA and PSCA derived peptides that are known to induce cytotoxic T lymphocytes responses were loaded into DCs for vaccination. In some patients, a cell penetrating peptide HIV tat protein sequence was also added to test its benefit in prolonging antigen presentation.

In this single-center open-label prospective phase I/II trial, 12 patients with androgen-independent CaP who failed at least one chemotherapy regimen were enrolled. Patients were immunized 4 times with PSA-, PSCA-, and HIV gag loaded DCs in biweekly intervals. Responses were assessed 2 weeks after the 4th injection. To assess patients' immune status, hepatitis B vaccinations were administered on day 1 and 43 followed by testing for anti-HB antibodies 2 weeks later. Testing of delayed-type hypersensitivity (DTH) was done using loaded and unloaded DCs administered intracutaneously on days 1 and 43 followed by photodocumentation 3 days later.

Median pretreatment PSA was 169ng/ml. Ten patients received at least 3 vaccinations. No patient developed a positive DTH reaction to unloaded DCs. Five patients developed DTH to PSCA only, 2 patients to PSA and PSCA and 1 patient to PSA, PSCA and HIV. There was no evidence of immediate or delayed toxicity in any patient. Six patients had stable disease (SD) and 5 of these received a median of 2 additional vaccinations until progression. Two patients received only 3 vaccinations due to early disease progression and 4 patients had progression after 4 vaccinations. Median survival of patients with documented DTH responses was 22 months, which was significantly superior to the overall survival of the remaining patients (8 months). There was no correlation between clinical or cellular responses and peripheral blood lymphocyte phenotype at baseline, number or immunophenotype of administered DC, or vaccination with HIV gag peptide.

A positive DTH to the vaccine was associated with significantly superior overall survival in this trial. Further testing is warranted.

By Christopher P. Evans, M.D.

Int J Cancer 2006;epub DOI: 10.1002/ijc.22097
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