Dexamethasone did not suppress immune boosting by personalized peptide vaccination for advanced prostate cancer patients

Abstract

Vaccination combined with dexamethasone could be recommended for further clinical trials from both immunological and clinical points of view.

Assessment of immunological biomarkers in patients with advanced cancer treated by personalized peptide vaccination

“…The levels of anti-peptide IgG were measured using the Luminex TM system, as previously reported. [25][26][27][28][29]45 In brief, plasma was incubated with 25 μl of peptide-coupled color-coded beads for 2 h at room temperature on a plate shaker. After incubation, the mixture was washed with a vacuum manifold apparatus and incubated with 100 μl of biotinylated goat anti-human IgG (chain-specific) for 1 h at room temperature.…”

“…Personalized peptide vaccination is based on a prevaccination measurement of peptide-specific CTL precursors and anti-peptide IgG in the circulation of cancer patients reactive to vaccine candidates, followed by administration of only reactive peptides (up to four peptides) as reported previously. [25][26][27][28][29] Selected peptides were mixed with incomplete Freund's adjuvant (Montanide ISA-51VG; Seppic, Paris, France), and four peptides of 1.5 ml emulsion each at doses of 3 mg/peptide were injected subcutaneously into the regional lymph node area. A total of 77 candidate peptides (32 peptides for HLA-A24-positive cancer patients, 37 for HLA-A2 and 8 for HLA-A3 supertypes) were used in the personalized peptide vaccination.…”

“…All of these peptides can induce HLA-A24-, A2-and A3-supertype-restricted and tumorspecific CTL activity in PBMCs of cancer patients. 6,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][42][43][44] Before the first vaccination and 7 days after every sixth vaccination, 30 ml of peripheral blood was obtained and PBMCs were isolated by means of Ficoll-Conray density gradient centrifugation. Peptide-specific CTL precursors in PBMCs were detected using the previously reported culture method.…”

“…These symptoms were manageable through routine interventions as reported previously. [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] The best response to the personalized peptide vaccination was assessed in 436 patients. No complete responses (CR) were observed in either group.…”

Sipuleucel-T for the treatment of metastatic prostate cancer

“…To this end, a small study of CRPC patients in Japan found that dexamethasone did not suppress immune boosting while prednisolone was able to suppress the immune response. 70 Ultimately, further studies will be required to better characterize the effects of steroids and chemotherapy on the efficacy of immunotherapies for cancer patients.…”