Immunological evaluation of personalized peptide vaccination in combination with UFT and UZEL for metastatic colorectal carcinoma patients

Hattori, Takashi; Mizutani, Takashi; Komatsu, Nobukazu; Yamada, Akira; Itoh, Kyogo; Shiozaki, Hitoshi; Okuno, Kiyotaka

doi:10.1007/s00262-009-0695-6

Cited by 43 publications

(54 citation statements)

References 22 publications

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“…To date, phase I cancer immunotherapy clinical studies that targeted the WT1 protein have been conducted for AML, MDS, lung, and breast cancer (22,23,31) and phase I/II clinical studies using WT1 peptides have been conducted for patients with various types of cancer (29). It was reported that the increase in the numbers of WT1-specific CTLs in cancer patients after vaccination with WT1 peptides closely correlates with the therapeutic efficacy against cancer (7,16,17,20). Therefore, monitoring antitumor immune responses, particularly the generation of tumor-specific CTLs, is critical for accurate assessments of the efficacy of cancer vaccine immunotherapy.…”

Section: Methodsmentioning

confidence: 99%

“…It has been reported that cancer vaccine therapy with short peptides induces increased cancer antigen-specific CTLs and maintains long stable disease in the cancer patients. However, vaccine therapy using short peptides still has numerous issues that need to be resolved for treating cancers (7,27,28). Thus, it is necessary to develop more efficient cancer vaccines and establish accurate methods to evaluate cancer antigen-specific immune responses in patients.…”

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confidence: 99%

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Establishment of a stable T lymphoma cell line transduced with HLA-A^|^lowast;24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring

et al. 2013

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Wilms' tumor gene 1 (WT1) has been proposed as an attractive target for cancer immunotherapy. A natural 9-mer peptide (CYTWNQMNL), which bound to human leukocyte antigen (HLA)-A*24:02, was identified from among WT1-specific cytotoxic T lymphocyte (CTL) epitopes. This natural WT1 CTL epitope peptide was further modified (CMTWNQMNL) to enhance its binding affinity to HLA-A*24:02. This modified WT1 CTL epitope peptide was superior to the natural peptide for inducing HLA-A*24:02-restricted WT1-specific CTLs. Here we induced several WT1 CTLs that reacted with both modified and natural WT1 tetramers from peripheral blood mononuclear cells. Then, T-cell receptor (TCR) genes were isolated from these WT1 CTLs to determine their Vα and Vβ usage. These TCR genes were transduced into human T lymphoma cells to establish a stable cell line, SK37, which expressed a WT1-specific TCR. We confirmed that SK37 cells reacted with both modified and natural WT1 tetramers, which indicated that SK37 cells could be a useful tool for WT1 tetramer reagent quality assurance. One the basis of these findings, we propose that this WT1 tetramer, which was quality-assured using established SK37 cells, will contribute to reliable immunomonitoring of tumor-specific CTL responses of cancer patients who receive WT1-targeted cancer vaccine therapy or TCR-gene therapy.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Establishment of a stable T lymphoma cell line transduced with HLA-A^|^lowast;24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring

et al. 2013

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“…The number of administered vaccinations varied widely, from 3 to 112 per patient, with the most prolonged vaccination periods being for the prostate cancer patients. Most of the safety, immune, as well as clinical responses in these studies have been previously reported (5)(6)(7)(8)(9)(10)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Studies are currently underway to obtain vaccination results for the treatment of pancreatic and breast cancer, as well as for the HLA-A3 supertype-positive patients.…”

Section: Methodsmentioning

confidence: 99%

Characteristics of severe adverse events after peptide vaccination for advanced cancer patients: Analysis of 500 cases

Yoshida

Noguchi²,

Mizutani³

et al. 2010

Oncol Rep

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Abstract. The purpose of this study was to investigate severe adverse events (SAEs) after therapeutic peptide vaccination for advanced cancer patients. We investigated SAEs following personalized peptide vaccinations in 500 advanced cancer patients, including 174 prostate, 74 colon, 51 pancreatic and 43 gastric cancer patients. The number of vaccination cycles varied widely, from 3 to 112. The severity of adverse events was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3, and events with a grade of >3 were defined as SAEs and were evaluated by the Institutional Safety Evaluation Committee. A total of 215 SAEs in 102 patients were recorded during the vaccine trials. The main causes for these events were cancer progression (152 SAEs in 78 patients), combined cancer treatments other than vaccination (35 in 21 patients), diseases other than cancer (20 in 19 patients), peptide vaccines (6 in 6 patients) and suicide (1 in 1 patient). The 6 vaccine-related SAEs, all grade 3, consisted of skin reactions at each injection site, cellulitis around the injection site, edemas of the head and neck regions, colitis, rectal bleeding and bladder-vaginal fistulae. Both cellular and humoral responses to the vaccinated peptides were highly boosted in all 6 of these patients, indicating the involvement of augmented immune responses in these SAEs. The clinical responses in these 6 patients consisted of 2 partial responses and 4 stable diseases. The majority of SAEs after peptide vaccination for advanced cancer patients were caused by cancer progression. The appearance of vaccine-related SAEs, except inflammatory injection site reactions, was unexpected, and fortunately the incidence was very low. Our results suggest that physicians should be on guard for these rare SAEs associated with augmented immune responses.

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“…We developed a new approach of peptide-based vaccination, named personalized peptide vaccination (PPV), in which vaccine antigens are selected and administered based on preexisting host immunity before vaccination (6)(7)(8)(9)(10)(11)(12)(13)(14). We have shown promising results of PPV in various types of advanced cancers (6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

“…We have shown promising results of PPV in various types of advanced cancers (6)(7)(8)(9). For example, a recently conducted randomized clinical trial of PPV for patients with advanced prostate cancer suggested a potentially favorable clinical outcome in the vaccinated group (9).…”

Section: Introductionmentioning

confidence: 99%

Personalized peptide vaccination in patients with refractory non-small cell lung cancer

et al. 2012

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Abstract. Since the prognosis of non-small cell lung cancer (NSCLC) remains poor, the development of novel therapeutic approaches, including cancer vaccines, is highly desirable. In the current study, we conducted a phase II study of personalized peptide vaccination (PPV), in which a maximum of 4 peptides were selected based on pre-existing humoral immune responses and administered subcutaneously (weekly for 6 consecutive weeks and bi-weekly thereafter) in refractory NSCLC patients. Forty-one refractory NSCLC patients (4 stage IIIb, 22 stage IV and 15 recurrent), who had failed to respond to chemotherapy and/or targeted therapy (median number of regimens, 3; median duration, 10 months), were enrolled. Median overall survival (OS) was 304 days with a one-year survival rate of 42% in the enrolled patients. The main toxicity of PPV was skin reactions at the injection sites, but no serious adverse events were observed. In order to identify potential biomarkers for predicting OS, pre-vaccination and post-vaccination clinical findings and laboratory data were retrospectively assessed and evaluated by multivariate Cox regression analysis. Among the pre-vaccination factors examined, high C-reactive protein (CRP) level was a significant predictor of unfavorable OS [hazard ratio (HR)=10.115, 95% confidence interval (CI)=2.447-41.806, P=0.001]. Among the post-vaccination factors, high CRP level and low frequency of CD3 + CD26 + cells were significant predictors of unfavorable OS (HR=23.127, P=0.003; HR=0.952, P= 0.012). Taken together, our results suggest the feasibility of PPV for the treatment of refractory NSCLC. Evaluation of the identified factors before or at an early stage of vaccination could be potentially useful for selecting NSCLC patients who would likely have better prognosis following PPV.

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Immunological evaluation of personalized peptide vaccination in combination with UFT and UZEL for metastatic colorectal carcinoma patients

Cited by 43 publications

References 22 publications

Establishment of a stable T lymphoma cell line transduced with HLA-A^|^lowast;24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring

Establishment of a stable T lymphoma cell line transduced with HLA-A^|^lowast;24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring

Characteristics of severe adverse events after peptide vaccination for advanced cancer patients: Analysis of 500 cases

Personalized peptide vaccination in patients with refractory non-small cell lung cancer

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