Realizing the basis for generating long-lasting clinical responses in
cancer patients after therapeutic vaccinations provides the means to further ameliorate clinical efficacy.
Peptide cancer vaccines stimulating CD4(+) T helper cells are often promising for inducing immunological memory and persistent CD8(+) cytotoxic T cell responses. Recent reports from our clinical trial with the
AE37 vaccine, which is a HER2 hybrid
polypeptide, documented its efficacy to induce CD4(+) T cell immunity, which was associated with clinical improvements preferentially among
HLA-DRB1*11(+)
prostate cancer patients. Here, we performed in-depth investigation of the CD4(+) T cell response against the
AE37 vaccine. We used the DR11/AE37 tetramer in combination with multicolor flow cytometry to identify and characterize AE37-specific CD4(+) T cells regarding memory and Tregs phenotype in
HLA-DRB1*11(+) vaccinated patients. To verify
vaccine-specific immunological memory in vivo, we also assessed AE37-specific CD4(+) T cells in defined CD4(+) memory subsets by cell sorting. Finally,
vaccine-induced AE37-specific CD4(+) T cells were assessed regarding their functional profile. AE37-specific memory CD4(+) T cells could be detected in
peptide-stimulated cultures from
prostate cancer patients following vaccination even 4 y post-vaccination. The vast majority of
vaccine-induced AE37-specific CD4(+) T cells exhibited a multifunctional, mostly Th1
cytokine signature, with the potential of
granzyme B production. In contrast, we found relatively low frequencies of Tregs among AE37-specific CD4(+) T cells. This is the first report on the identification of
vaccine-induced HER2-specific multifunctional long-lasting CD4(+) T cells in vaccinated
prostate cancer patients.