Identification of peptides applicable as vaccines for HLA‐A26‐positive cancer patients

Niu, Yamei; Terasaki, Yasunobu; Komatsu, Nobukazu; Noguchi, Masanori; Shichijo, Shigeki; Itoh, Kyogo

doi:10.1111/j.1349-7006.2009.01298.x

Cited by 5 publications

(13 citation statements)

References 16 publications

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“…Dendritic cells pulsed with this peptide in a cocktail elicited responses from patients' lymphocytes responding to antigen-pulsed DC by positive ELISPOTs. Whsc2 mRNA was initially discovered to be made by gliomas and CTLs could be developed that responded towards glioma cells [39], [53]. By proteomic studies and confirmed by western blotting, Whsc2 was found to be heavily expressed in gliomas, but not in normal tissue [54].…”

Section: Discussionmentioning

confidence: 99%

Differential Glioma-Associated Tumor Antigen Expression Profiles of Human Glioma Cells Grown in Hypoxia

Ge¹,

Cornforth²,

Hoa

et al. 2012

PLoS ONE

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Human U251 and D54 glioma cells were tested for expression of 25 glioma-associated tumor antigen precursor proteins (TAPP) under hypoxic (1% O2) or normoxic (21% O2) conditions. Hypoxic glioma cell lines increased their mRNA expression for nine TAPP (Aim2, Art-4, EphA2, EZH2, Fosl1, PTH-rP, Sox 11, Whsc2 and YKL-40), as assessed by quantitative reverse transcriptase real-time/polymerase chain reaction (qRT-PCR). Increased differences with three hypoxic-induced TAPP: EZH2, Whsc2 and YKL-40 were shown at the protein levels by fluorescent antibody staining and quantitative electrophoretic analysis. Two TAPP (MRP3 and Trp1) were down-regulated by hypoxia in glioma cell lines. Growing the glioma cells under hypoxia for 13 days, followed by returning them back to normoxic conditions for 7 days, and restored the original normoxic TAPP profile. Thus, hypoxia was an environmental factor that stimulated the transient expression of these antigens. Intracranial xenografts grown in nude mice derived from U251 cells that had been cultured under neurosphere stem cell conditions showed increased expression of Whsc2 or YKL-40, demonstrating that these in vitro properties of glioma also occur in vivo. Whsc2-specific cytotoxic T lymphocytes killed the hypoxic U251 glioma cells better than normoxic glioma cells. The antigens expressed by hypoxic tumor cells may be a better source of starting tumor material for loading dendritic cells for novel immunotherapy of glioma using tumor-associated antigens.

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Section: Discussionmentioning

confidence: 99%

Differential Glioma-Associated Tumor Antigen Expression Profiles of Human Glioma Cells Grown in Hypoxia

Ge¹,

Cornforth²,

Hoa

et al. 2012

PLoS ONE

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“…To the best of our knowledge, this is the first clinical trial of peptide‐based cancer vaccines for HLA‐A26 + cancer patients. The HLA‐A26 allele is found in approximately 11% of the Japanese population and includes various genotypes . The frequencies of the different HLA‐A26 genotypes in the Japanese population have been reported as follows: HLA‐A2601: 7.35%; HLA‐A2603: 2.23%; HLA‐A2603: 1.81%; HLA‐A2605: 0.07%; and HLA‐A2606: 0.01% .…”

Section: Discussionmentioning

confidence: 99%

“…One of them could be deletion or depression of the expression of HLA‐A26 molecules on the surface of cancer cells from these HLA‐A26 homogenous advanced cancer patients. PBMCs from HLA‐A26 heterogeneous advanced cancer patients were provided for in vitro determination of these 4 peptides that could induce peptide‐specific CTL activity for HLA‐A26 + cancer patients as reported previously . Their clinical stages were not as advanced as to those of the 21 patients who received PPV in this study.…”

Section: Discussionmentioning

confidence: 99%

“…To develop cancer vaccines applicable for these minor HLA‐A alleles, we previously identified large numbers of CTL epitope peptides from alleles other than A2 or A24, and some of them were provided for the clinical trials of peptide vaccines for the HLA‐A3 superfamily (HLA‐A11, ‐A31, and ‐A33) or HLA‐A26 + cancer patients under PPV regimens in the past 7 years . The HLA‐A26 allele is found in approximately 11% of the Japanese population, 4% of the Caucasian population in the USA, and 7.5% of the African population of Cape Town …”

mentioning

confidence: 99%

“…(8) Although many clinical trials of peptide-based cancer vaccines for HLA-A2 + and HLA-A24 + cancer patients have been carried out in the past two decades, cancer patients with the other alleles, including HLA-A1, -A3, -A11, -A26, -A31, or -A33, were excluded from these clinical trials because of the relatively lower allele expression worldwide. (9,10) To develop cancer vaccines applicable for these minor HLA-A alleles, we previously identified large numbers of CTL epitope peptides from alleles other than A2 or A24, and some of them were provided for the clinical trials of peptide vaccines for the HLA-A3 superfamily (HLA-A11, -A31, and -A33) or HLA-A26 + cancer patients under PPV regimens in the past 7 years. (11,12) The HLA-A26 allele is found in approximately 11% of the Japanese population, 4% of the Caucasian population in the USA, and 7.5% of the African population of Cape Town.…”

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confidence: 99%

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

et al. 2015

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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.

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T cells in SARS-CoV-2 infection and vaccination

Young¹

2022

Therapeutic Advances in Vaccines and Immunotherapy

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While antibodies garner the lion’s share of attention in SARS-CoV-2 immunity, cellular immunity (T cells) may be equally, if not more important, in controlling infection. Both CD8+ and CD4+ T cells are elicited earlier and are associated with milder disease, than antibodies, and T-cell activation appears to be necessary for control of infection. Variants of concern (VOCs) such as Omicron have escaped the neutralizing antibody responses after two mRNA vaccine doses, but T-cell immunity is largely intact. The breadth and patient-specific nature of the latter offers a formidable line of defense that can limit the severity of illness, and are likely to be responsible for most of the protection from natural infection or vaccination against VOCs which have evaded the antibody response. Comprehensive searches for T-cell epitopes, T-cell activation from infection and vaccination of specific patient groups, and elicitation of cellular immunity by various alternative vaccine modalities are here reviewed. Development of vaccines that specifically target T cells is called for, to meet the needs of patient groups for whom cellular immunity is weaker, such as the elderly and the immunosuppressed. While VOCs have not yet fully escaped T-cell immunity elicited by natural infection and vaccines, some early reports of partial escape suggest that future VOCs may achieve the dreaded result, dislodging a substantial proportion of cellular immunity, enough to cause a grave public health burden. A proactive, rather than reactive, solution which identifies and targets immutable sequences in SARS-CoV-2, not just those which are conserved, may be the only recourse humankind has to disarm these future VOCs before they disarm us.

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Identification of peptides applicable as vaccines for HLA‐A26‐positive cancer patients

Cited by 5 publications

References 16 publications

Differential Glioma-Associated Tumor Antigen Expression Profiles of Human Glioma Cells Grown in Hypoxia

Differential Glioma-Associated Tumor Antigen Expression Profiles of Human Glioma Cells Grown in Hypoxia

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

T cells in SARS-CoV-2 infection and vaccination

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