Background:
Although numerous clinical studies of peptide-based cancer vaccine were conducted in the past two decades, no sufficient outcome for drug approval was obtained at the present time.
Aim:
To evaluate the safety and immune responses of a cancer vaccine consisting of 20 mixed peptides (KRM-20) in patients with castration-resistant prostate cancer (CRPC).
Methods:
Patients received each of the randomly assigned three different doses of KRM-20 (6 mg/0.15 ml, 20 mg/0.5 ml or 60 mg/1.5 ml) once a week for 6 weeks. KRM-20 was applicable for patients with HLA-A2, A3, A11, A24, A26, A31, or A33 allele, covering the vast majority of population worldwide. Each group consisted of 5 patients. Peptide-specific cytotoxic T-lymphocyte (CTL) and immunoglobulin G (IgG) response, along with frequency of myeloid-derived suppressor cells (MDSC) and regulatory T cells were measured.
Results:
No serious adverse drug reactions were encountered. CTL response after 3rd vaccination was boosted for 3 of 59, 12 of 46, and 11 of 59 peptides tested in patients receiving 6, 20, and 60mg KRM-20, respectively. CTL response after 6th vaccination, however, largely decreased in patients receiving 60mg, in concomitant with strong boosting of IgG response. Frequency of regulatory T cells after 3rd or 6th vaccination was increased in 3 of 5 patients receiving 60mg or 6 mg KRM-20, respectively. Frequency of MDSC inversely correlated with CTL activity in patients receiving 20 mg KRM-20. Clinical responses determined by PSA levels were 2PR (from 20 mg group), 5SD, and 10 PD.
Conclusions:
Twenty mg of KRM-20 could be recommended for a phase II study primarily because of lower levels of vaccine-induced suppression to CTL activity.