CD4+ T Cell Epitope Discovery and Rational Vaccine Design

Rosa, Daniela Santoro; Ribeiro, Susan Pereira; Cunha-Neto, Edécio

doi:10.1007/s00005-010-0067-0

Cited by 71 publications

(59 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Granulocytic MDSCs may be a core population of neutrophils which may suppress antitumor immunity. Previously, there have been some reports describing the advantage of the use of HLA-class Ⅱ-restricted antigen epitope(s) [33] , while it is also suggested the possibility that HLA-class Ⅱ-restricted epitope may induce suppressive immune responses such as Th2, Th17 and Tregs. I believe that it is reasonable and useful to make a cancer vaccine using the DCs optimized ex vivo for Th1-inducing type.…”

Section: Clinical Effects Of the Vaccell Mainly In Pancreatic Cancermentioning

confidence: 99%

Dendritic cell-based vaccine for pancreatic cancer in Japan

Okamoto

Kobayashi

Yonemitsu

et al. 2016

WJGPT

View full text Add to dashboard Cite

Abstract"Vaccell" is a dendritic cell (DC)-based cancer vaccine which has been established in Japan. The DCs play central roles in deciding the direction of host immune reactions as well as antigen presentation. We have demonstrated that DCs treated with a streptococcal immune adjuvant OK-432, produce interleukin-12, induce Th1-dominant state, and elicit anti-tumor effects, more powerful than those treated with the known DCmaturating factors. We therefore decided to mature DCs by the OK-432 for making an effective DC vaccine, Vaccell. The 255 patients with inoperable pancreatic cancer who received standard chemotherapy combined with DC vaccines, were analyzed retrospectively. Survival time of the patients with positive delayed type hypersensitivity (DTH) skin reaction was significantly prolonged as compared with that of the patients with negative DTH. The findings strongly suggest that there may be "Responders" for the DC vaccine in advanced pancreatic cancer patients. We next conducted a smallscale prospective clinical study. In this trial, we pulsed HLA class Ⅱ-restricted WT1 peptide (WT1-Ⅱ) in addition to HLA class Ⅰ-restricted peptide (WT1-Ⅰ) into the DCs. Survival of the patients received WT1-Ⅰ and -Ⅱ pulsed DC vaccine was significantly extended as compared to that of the patients received DCs pulsed with WT1-Ⅰ or WT1-Ⅱ alone. Furthermore, WT1-specific DTH positive patients showed significantly improved the overall survival as well as progressionfree survival as compared to the DTH negative patients. may be associated with a good clinical outcome in advanced pancreatic cancer. We are now planning a pivotal study of the Vaccell in appropriate protocols in Japan.

show abstract

Section: Clinical Effects Of the Vaccell Mainly In Pancreatic Cancermentioning

confidence: 99%

Dendritic cell-based vaccine for pancreatic cancer in Japan

Okamoto

Kobayashi

Yonemitsu

et al. 2016

WJGPT

View full text Add to dashboard Cite

show abstract

“…26 Accordingly, the discovery and inclusion of appropriate CD4+ T-cell epitopes is considered paramount in epitope-base vaccine design, because cognate help provided by CD4+ T-cells is essential for the generation of vigorous humoral and cellular responses by promoting optimal expansion of CD8+ cytotoxic T-cells, generating and maintaining T-cell memory and promoting B-cell differentiation. 27 This necessity is underscored by the disappointing results of a large phase-II clinical trial of an HIV vaccine that elicited only CD8+ cytotoxic T-cell responses unable to prevent HIV-1 infection, 28 and a phase-III clinical trial of an HIV vaccine that stimulated an antibody response also did not correlate with the incidence of HIV-1 infection. 29 In addition, the critical role of CD4+ T-helper cells in effective HIV-specific immunity has been documented using HIV-infected individuals where loss of these cells was noted as the hallmark symptom of disease.…”

Section: Dealing With Hiv-1 Genetic Diversitymentioning

confidence: 99%

Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production

Oyarzún

Kobe

2015

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

Novel vaccination approaches based on rational design of B-and T-cell epitopes -epitope-based vaccinesare making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B-and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.

show abstract

“…[9][10][11][12][13][14] Evidence from human and animal studies has indicated that optimal cancer vaccines require the participation of both CD4 + and CD8 + T cells. [15][16][17] A recent report highlighted the successful use of tumorassociated antigen-specific CD4 T-cell clones as therapeutic agents in the treatment of melanoma. 18 We initially identified PASD1 as a tumor-associated antigen in DLBCL 19 and acute myeloid leukemia 20 while later studies showed PASD1 to be a novel cancer-testis antigen expressed in a wide range of hematologic malignancies.…”

Section: Introductionmentioning

confidence: 99%

CD4-positive T-helper cell responses to the PASD1 protein in patients with diffuse large B-cell lymphoma

Ait-Tahar¹,

Liggins²,

Collins³

et al. 2010

Haematologica

View full text Add to dashboard Cite

BackgroundVaccine development targeting the novel immunogenic Per ARNT Sim Domain containing 1 (PASD1) cancer testis antigen represents an attractive therapeutic approach for the significant number of patients with diffuse large B-cell lymphoma who are refractory to conventional treatment. Since CD4-positive T helper cells have crucial roles in promoting and maintaining immune responses to tumor antigens, the presence of a CD4-positive T-helper immune response to the PASD1 antigen in patients with diffuse large B-cell lymphoma was investigated in the current study. Design and MethodsThirty-one patients with diffuse large B-cell lymphoma (25 with de novo, five with transformed and one with T-cell-rich B-cell lymphoma) were studied. Five immunogenic PASD1 peptides predicted to bind to several major histocompatibiliy complex, class II DR beta 1 alleles were identified using web-based algorithms. Peripheral blood mononuclear cells from patients were used to investigate the immunogenicity of these DR beta 1-restricted peptides in vitro using both gamma-interferon release enzyme-linked immunospot and cytolytic assays. ResultsTwo of the five PASD1 peptides, PASD1(6) and PASD1(7), were shown to be immunogenic in 14 out of 32 patients studied in a gamma-interferon release assay. CD4-positive T-helper cell lines from two patients raised against PASD1 peptides were able to lyse cell lines derived from hematologic malignancies expressing endogenous PASD1 protein. ConclusionsThis is the first report of a CD4-positive T-helper response to the PASD1 protein in patients with lymphoma. The immunogenic peptides described here represent valuable additional candidates for inclusion in a vaccine to treat patients with PASD1-positive diffuse large B-cell lymphoma whose disease is refractory to conventional therapies. -cell lymphoma. Haematologica 2011;96(1):78-86. doi:10.3324/haematol.2010 This is an open-access paper. CD4-positive T-helper cell responses to the PASD1 protein in patients with diffuse large B-cell lymphoma

show abstract

CD4+ T Cell Epitope Discovery and Rational Vaccine Design

Cited by 71 publications

References 87 publications

Dendritic cell-based vaccine for pancreatic cancer in Japan

Dendritic cell-based vaccine for pancreatic cancer in Japan

Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production

CD4-positive T-helper cell responses to the PASD1 protein in patients with diffuse large B-cell lymphoma

Contact Info

Product

Resources

About