Enhanced multiepitope-based vaccines elicit CD8+ cytotoxic T cells against both immunodominant and cryptic epitopes

Tine, John A.; Firat, Hüseyin; Payne, Anne F.; Russo, G.A.; Davis, Stephen W.; Tartaglia, Jim; Lefrère, François; Demoyen, Pierre Langlade; Moingeon, Philippe

doi:10.1016/j.vaccine.2003.01.001

Cited by 23 publications

(16 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In clinical trials, the proportion of TAA-specific T cells can be as high as 3%, as determined by Melan-A analogue peptide [26][27][28][29][30][31][32][33][34][35] multimer staining (3), or 8.89% by gp100 209-2M tetramer staining (25). However, one can claim that further increase in the amount of TAA-specific T cells would eventually cause tumor rejectionthat is the premise of antitumor immunology.…”

Section: Discussionmentioning

confidence: 99%

“…The variables are many and include the immunogenicity of the TAA, the presentation of the TAA on the tumor, the number of TAA-specific precursor CTLs in the patient, the site and mode of immunization or the timing of adoptive transfer, and the potential ease by which the specific TAA may be silenced. Quantification of CD8 immune responses upon immunization with more than one epitope reveals this complexity (28,32,33). It is possible that there is a threshold number of TAAs required for the rejection of a particular tumor, but this number and the exact nature of these TAAs are unclear.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Exuberated Numbers of Tumor-Specific T Cells Result in Tumor Escape

Goldberger

Volovitz

Machlenkin³

et al. 2008

Cancer Research

View full text Add to dashboard Cite

Cytotoxic T cells (CTL) play a major role in tumor rejection. Expansion of CTLs, either by immunization or adoptive transfer, is a prominent goal in current immunotherapy. The antigen-specific nature of these expansion processes inevitably initiates a clonotypic attack on the tumor. By injecting an Ovalbumin-expressing melanoma into OT-I mice, in which >90% of CTLs recognize an Ovalbumin peptide, we show that an increased number of tumor-specific CTLs causes emergence of escape variants. We show that these escape variants are a result of antigen silencing via a yet undetermined epigenetic mechanism, which occurs frequently and is spontaneously reversible. We further show that an increase in the time of tumor onset in OT-I compared with C57BL/6J is a result of immune selection. [Cancer Res 2008;68(9):3450-7]

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Exuberated Numbers of Tumor-Specific T Cells Result in Tumor Escape

Goldberger

Volovitz

Machlenkin³

et al. 2008

Cancer Research

View full text Add to dashboard Cite

show abstract

“…Specific immune responses enhancement was achieved by introducing minigenes encoding CD8 + epitopes into Ad vectors which bring strong helper signals (Tatsis and Ertl, 2004). Minigenes were reported to be more efficient than full-length protein constructs for eliciting CTL responses (Tine et al, 2005), likely because proteasomal processing is not required before association with MHC class I molecules, thus optimizing antigen delivery (Leifert et al, 2004). 168NP was selected for minigenes construction based on its capacity stimulates a CD8 + cytolytic repertoire which recognized a natural peptide nearly as well as the NP-modified one.…”

Section: Discussionmentioning

confidence: 99%

Prolongation of prion disease-associated symptomatic phase relates to CD3+ T cell recruitment into the CNS in murine scrapie-infected mice

Sacquin

Chaigneau

Defaweux

et al. 2012

Brain, Behavior, and Immunity

View full text Add to dashboard Cite

a b s t r a c tPrion diseases are caused by the transconformation of the host cellular prion protein PrP c into an infectious neurotoxic isoform called PrP Sc . While vaccine-induced PrP-specific CD4 + T cells and antibodies partially protect scrapie-infected mice from disease, the potential autoreactivity of CD8 + cytotoxic T lymphocytes (CTLs) received little attention. Beneficial or pathogenic influence of PrP c -specific CTL was evaluated by stimulating a CD8 + T-cell-only response against PrP in scrapie-infected C57BL/6 mice. To circumvent immune tolerance to PrP, five PrP-derived nonamer peptides identified using prediction algorithms were anchored-optimized to improve binding affinity for H-2D b and immunogenicity (NP-peptides). All of the NP-peptides elicited a significant number of IFNc secreting CD8 + T cells that better recognized the NP-peptides than the natives; three of them induced T cells that were lytic in vivo for NP-peptide-loaded target cells. Peptides 168 and 192 were naturally processed and presented by the 1C11 neuronal cell line. Minigenes encoding immunogenic NP-peptides inserted into adenovirus (rAds) vectors enhanced the specific CD8 + T-cell responses. Immunization with rAd encoding 168NP before scrapie inoculation significantly prolonged the survival of infected mice. This effect was attributable to a significant lengthening of the symptomatic phase and was associated with enhanced CD3 + T cell recruitment to the CNS. However, immunization with Ad168NP in scrapie-incubating mice induced IFNc-secreting CD8 + T cells that were not cytolytic in vivo and did not influence disease progression nor infiltrated the brain. In conclusion, the data suggest that vaccine-induced PrP-specific CD8 + T cells interact with prions into the CNS during the clinical phase of the disease.

show abstract

“…Another polyepitope, produced in poxvirus and containing ten HLA-A2-restricted epitopes derived from five melanoma antigens, elicited a CTL response in vitro (33). The advantage of using antigens with point mutations to improve peptide-MHC binding has also been demonstrated (34).…”

Section: Discussionmentioning

confidence: 99%

A melanoma multiepitope polypeptide induces specific CD8+ T-cell response

Levy

Pitcovski

Frankenburg

et al. 2007

Cellular Immunology

View full text Add to dashboard Cite

Strategies using epitope-based vaccination are being considered for melanoma immunotherapy, in an attempt to overcome failure of other modalities. In the present study, we designed and produced a multiepitope polypeptide for melanoma (MEP-mel), which contains three repeats of four antigenic epitopes (gp100:209-217 (210M); gp100:280-288 (288V); Mart1:26-35 (27L); tyrosinase: 368-376 (370D). The peptides were attached to each other by linkers containing sequences recognized by the proteasome, to improve protein cleavage and antigen presentation. The results show that peptidespecific T cells produced IFN-γ when stimulated with MEP-mel-transfected dendritic cells. The presentation of peptides by MEP-mel-transfected dendritic cells was proteasome-dependent and was more long-lasting than the presentation of exogenously delivered native peptides. When dendritic cells were loaded with MEP-mel protein, weak cross presentation was induced. The production of multiepitope molecules based on several peptides linked by sequences sensitive to proteasomal cleavage represents a promising new tool for the improvement of cancer immunotherapy.

show abstract

Enhanced multiepitope-based vaccines elicit CD8+ cytotoxic T cells against both immunodominant and cryptic epitopes

Cited by 23 publications

References 30 publications

Exuberated Numbers of Tumor-Specific T Cells Result in Tumor Escape

Exuberated Numbers of Tumor-Specific T Cells Result in Tumor Escape

Prolongation of prion disease-associated symptomatic phase relates to CD3+ T cell recruitment into the CNS in murine scrapie-infected mice

A melanoma multiepitope polypeptide induces specific CD8+ T-cell response

Contact Info

Product

Resources

About