Immunological evaluation of peptide vaccination for cancer patients with the HLA‐A26 allele

Abstract

To develop a peptide vaccine for cancer patients with the HLA-A26 allele, which is a minor population worldwide, we investigated the immunological responses of HLA-A26+/A26+ cancer patients to four different CTL epitope peptides under personalized peptide vaccine regimens. In personalized peptide vaccine regimens, two to four peptides showing positive peptide-specific IgG responses in pre-vaccination plasma were selected from the four peptide candidates applicable for HLA-A26+/A26+ cancer patients and administered s.c. Peptide-specific CTL and IgG responses along with cytokine levels were measured before and after vaccination. Cell surface markers in PBMCs and plasma cytokine levels were also measured. In this study, 21 advanced cancer patients, including seven lung, three breast, two pancreas, and two colon cancer patients, were enrolled. Their HLA-A26 genotypes were HLA-A26:01 (n = 24), HLA-A26:03 (n = 10), and HLA-A26:02 (n = 8). One, 14, and 6 patients received two, three, and four peptides, respectively. Grade 1 or 2 skin reactions at the injection sites were observed in the majority of patients, but no severe adverse events related to the vaccination were observed. Peptide-specific CTL responses were augmented in 39% or 22% of patients after one or two cycles of vaccination, respectively. Notably, peptide-specific IgG were augmented in 63% or 100% of patients after one or two cycles of vaccination, respectively. Personalized peptide vaccines with these four CTL epitope peptides could be feasible for HLA-A26+ advanced cancer patients because of their safety and higher rates of immunological responses.

Predictive factors of the tumor immunological microenvironment for long‐term follow‐up in early stage breast cancer

“…The research investigating clinical biomarkers related to immunologic factors or TILs involving EBC is still insufficient. Our previous studies showed that the expression of FOXP3 on lymphocytes or tumor cells of EBC was significantly associated with clinical outcome and tumor‐specific immune responses, as well as the observation that clinical benefits in patients with metastatic BC could be augmented by peptide vaccines derived from various tumor‐associated antigens . In this study, we described the tumor environmental interaction between the density of TILs or macrophages and various immunologic molecules, including PD‐L1, PD‐1, and PTEN, by the intrinsic biological subtypes in EBC.…”

“…Breast cancer is traditionally thought of as a kind of low immunogenic carcinoma, but the influence of local immunologic factors on clinical outcome of BC is still under evaluation. It has been indicated that FOXP3 expression on lymphocytes and tumor cells of EBC is significantly associated with clinical outcome and that the peptide vaccines of tumor‐associated antigens could induce and boost tumor‐specific immune response in patients with metastatic BC . Novel investigations have shown that immunologic factors, such as TILs, and immune relevant factors, including PD‐1, PD‐L1, and PTEN, are significantly associated with responses to treatment and clinical outcome .…”

HLAPolymorphisms Are Associated with Treatment-Free Remission Following Discontinuation of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia

“…BCR-ABL1 chimeric proteins induce expansion of clonal human leucocyte antigen (HLA)-restricted cytotoxic T cells (CTL), which may control CML (19). Furthermore, the magnitude of HLA-restricted CTL depends on the HLA allele (20,21). In particular, HLA-A à 02:01, à 24:02, and à 11:01 can drive expansion of HLA-restricted cytotoxic T cells in patients with CML (22).…”

Evaluation of the immunological response of patients with childhood cancer treated with the personalized peptide vaccine for refractory soft tissue sarcoma: An early phase II study

“…For measuring the IgG responses to 31 peptides, IgG titers specific to the antigen peptides in the plasma were evaluated by using a bead-based multiplex Luminex assay, as previously described. [5][6][7][8][9][10][11][12] We adopted "Fluorescence Intensity Unit (FIU)" for measuring peptide-specific IgG response associated with personalized vaccine. Komatsu reported the comparison between the IgG measured by ELISA and FIU 12 .…”

“…8,9 Humoral responses against these 31 peptides-encoded by 15 different tumor-associated antigens-are detectable in healthy donors and cancer patients, and these levels were biomarkers for OS in not only vaccinated patients but also unvaccinated patients with advanced cancer. 10,11 However, little is known about the immunological features of patients with refractory childhood cancer considering the tumor immunology, partly owing to the lack of an affordable assay system to measure the preexisting antitumor immunity. Accordingly, we conducted the current early phase II clinical study for patients with refractory childhood cancer to evaluate the possible application of the PPV as a new immunotherapy modality.…”