Functional characterization of CTL against gp100 altered peptide ligands

Dionne, Sara O.; Smith, Margaret H.; Marincola, Francesco M.; Lake, Douglas F.

doi:10.1007/s00262-002-0358-3

Cited by 13 publications

(2 citation statements)

References 23 publications

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“…Heteroclitic peptide modifications to tumor antigen T cell epitopes have been described in the literature. Especially, replacement of the amino acid residue at position 2 to methionine has increased binding to HLA-A*02:01 and CTL-inducing ability of gp100 209–217 epitope ( Dionne et al, 2003 ; Rosenberg et al, 2005 ). It is interesting that the H3.3K27M hotspot mutation has a fortuitous substitution of methionine at position 27 (position 2 of the epitope peptide) that naturally generates a heteroclitic peptide with improved HLA-A2 binding and immunogenicity compared with the nonmutated H3.3WT peptide.…”

Section: Discussionmentioning

confidence: 99%

Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T cell therapy

Chheda

Kohanbash

Okada

et al. 2017

Journal of Experimental Medicine

185

166

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Section: Discussionmentioning

confidence: 99%

Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T cell therapy

Chheda

Kohanbash

Okada

et al. 2017

Journal of Experimental Medicine

185

166

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“…Peptides were chosen for studies based upon predicted strong binding to HLA-A* 0201. Binding affinity determinations of altered survivin peptides were performed as described by Dionne et al [12]. The affinity determination of SVN 53-67/M57 for HLA-A* 0201 was performed utilizing competitive peptide displacement assays.…”

Section: Methodsmentioning

confidence: 99%

Antitumor cytotoxic T-cell response induced by a survivin peptide mimic

Ciesielski

Ahluwalia

Munich

et al. 2010

Cancer Immunol Immunother

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Survivin is a tumor-associated antigen with significant potential as a cancer vaccine target. We have identified a survivin peptide mimic containing human MHC class I epitopes and a potential class II ligand that induces a potent antitumor response in C57BL/6 mice with GL261 cerebral gliomas. This peptide is able to elicit both CD8+ CTL and T helper cell responses in C57BL/6 mice. The corresponding region of the human survivin molecule represented by peptide SVN53-67 is 100% homologous to the murine protein, but SVN53-67 is weakly immunogenic in man. We evaluated several amino acid substitutions in putative human MHC I anchor positions in SVN53-67 to identify potential peptide mimics that could provide an enhanced antitumor immune response against human glioma and primary central nervous system lymphoma (PCNSL) cells in culture. We evaluated survivin peptides with predicted binding to human HLA-A*0201 antigen using peptide-loaded dendritic cells from PBMC of patients with these malignancies. One alteration (M57) led to binding to HLA-A*0201 with significantly higher affinity. We compared the ability of autologous dendritic cells loaded with SVN53-67 peptide and SVN53-67/M57 in CTL assays against allomatched and autologous, survivin-expressing, human malignant glioma and PCNSL cells. Both SVN53-67 and SVN53-67/M57 produced CTL-mediated killing of malignant target cells; however, SVN53-67/M57 was significantly more effective than SVN53-67. Thus, SVN53-67/M57 may act as a peptide mimic to induce an enhanced antitumor CTL response in tumor patients. The use of SVN53-67/M57 as a cancer vaccine might have application for cancer vaccine therapy.

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Spontaneous T cell responses to Epstein‐Barr virus‐encoded BARF1 protein and derived peptides in patients with nasopharyngeal carcinoma: Bases for improved immunotherapy

Martorelli

Houali

Caggiari

et al. 2008

Intl Journal of Cancer

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Immunotherapy approaches targeting Epstein-Barr virus (EBV)-encoded antigens induce objective clinical responses only in a fraction of patients with undifferentiated nasopharyngeal carcinoma (UNPC). In the present study, we have characterized the immunogenicity of the EBV-encoded BARF1 oncogene with the aim to assess whether this protein could constitute a new target antigen for immunotherapy in this setting. Spontaneous CD41 and CD81 T cell responses specific for the recombinant p29 BARF1 protein were detected by IFNc-ELISPOT in both EBV-seropositive donors and UNPC patients, but not in EBV-seronegative individuals. Using immunoinformatic prediction tools, we have selected 5 different candidate BARF1 T cell epitopes presented by HLA-A*0201. Although only one of these peptides was able to bind HLA-A2 with low affinity in the T2 stabilization assay, all 5 BARF1 nonamers readily elicited specific CD81 T cell responses in EBV-seropositive HLA-A*02011 donors and UNPC patients. Notably, the magnitude of CD81 T cell responses to the whole BARF1 protein and derived A*0201 peptides was significantly higher in UNPC patients than in healthy donors. Moreover, cytotoxic T lymphocytes specific for the p2-10, p23-31, or p49-57 BARF1 peptides were easily obtained from HLA-A*02011 donors. These cultures were not only able to lyse autologous targets loaded with the antigenic peptide, but also recognized tumor cells endogenously expressing BARF1 in an antigen-specific and HLA-A2-restricted manner. These findings, indicate that BARF1 is a particularly attractive antigen with immunogenic properties in most UNPC patients and provide valuable information to develop new strategies to improve the efficacy of EBV-targeting immunotherapy of UNPC patients.

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Functional characterization of CTL against gp100 altered peptide ligands

Cited by 13 publications

References 23 publications

Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T cell therapy

Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T cell therapy

Antitumor cytotoxic T-cell response induced by a survivin peptide mimic

Spontaneous T cell responses to Epstein‐Barr virus‐encoded BARF1 protein and derived peptides in patients with nasopharyngeal carcinoma: Bases for improved immunotherapy

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