Advances in the study of HLA-restricted epitope vaccines

Zhao, Lingxiao; Zhang, Min; Cong, Hua

doi:10.4161/hv.26088

Cited by 47 publications

(31 citation statements)

References 94 publications

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“…Combining peptide epitopes derived from more than one TAA may be more advantageous because it may enhance CTL induction and circumvent the potential of antigen escape which has been observed when all the peptide epitopes were derived from a single TAA . Also, it was reported in other studies that patients showing CTL response to multiple peptides had better median survival time and 1‐year survival rate as compared to cytotoxic chemotherapy . In addition, it was found that lower survival rates and more frequent metachronous metastases were observed in patients exhibiting higher RNF43 mRNA expression, and that RNF43 mRNA expression was significantly correlated with relapse after surgery .…”

Section: Discussionmentioning

confidence: 98%

“…The results of RNF43‐ and TOMM34‐derived peptide‐specific CTL and DTH responses across the cohorts indicated that an immune response was triggered by OCV‐C02. In this vaccination approach, peptide epitopes derived from TAA associate with the respective HLA molecules activating CTL to eliminate tumor cells directly or indirectly through the secretion of cytokines such as interferon‐gamma (IFN‐γ) and tumor necrosis factor‐alpha (TNF‐α) . Several studies involving the peptide epitopes of RNF43 and TOMM34 have shown that both are effective in inducing CTL .…”

Section: Discussionmentioning

confidence: 99%

“…As shown in the results of ELISpot and ICS assays for the main evaluation period of cycle 1, almost half of the total patients across the cohorts showed CTL response against either one or both peptides. Combining peptide epitopes derived from more than one TAA may be more advantageous because it may enhance CTL induction and circumvent the potential of antigen escape which has been observed when all the peptide epitopes were derived from a single TAA . Also, it was reported in other studies that patients showing CTL response to multiple peptides had better median survival time and 1‐year survival rate as compared to cytotoxic chemotherapy .…”

Section: Discussionmentioning

confidence: 99%

“…In this vaccination approach, peptide epitopes derived from TAA associate with the respective HLA molecules activating CTL to eliminate tumor cells directly or indirectly through the secretion of cytokines such as interferon-gamma (IFN-c) and tumor necrosis factor-alpha (TNF-a). (27) Several studies involving the peptide epitopes of RNF43 and TOMM34 have shown that both are effective in inducing CTL. (12,16,21) The exploratory analysis of this study showed no clear correlation between immunological responses and dose.…”

Section: Discussionmentioning

confidence: 99%

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Phase 1 study of OCV‐C02, a peptide vaccine consisting of two peptide epitopes for refractory metastatic colorectal cancer

et al. 2017

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Summary OCV‐C02 is a peptide vaccine consisting of two peptide epitopes derived from ring finger protein 43 (RNF43) and translocase of outer mitochondrial membrane 34 (TOMM34). This Phase 1 study assessed the safety, preliminary efficacy and immunological responses following OCV‐C02 administration in patients with advanced or relapsed colorectal cancer who were intolerant or refractory to standard chemotherapy. Primary endpoint was any occurrence of dose‐limiting toxicity (DLT) during cycle 1. Secondary endpoints were treatment‐emergent adverse events, efficacy and immunological responses. Efficacy was evaluated based on overall response rate, disease control rate, time to treatment failure and overall survival. Immunological responses were evaluated by measuring CTL, delayed‐type hypersensitivity (DTH) and regulatory T cells (Tregs). Twenty‐four patients who were HLA‐A*24:02‐positive were enrolled and grouped into four cohorts of six patients each: cohorts 1, 2, 3, and 4 which received s.c. OCV‐C02 (emulsifying agent: Montanide™ ISA 51 VG) 0.3, 1, 3, and 6 mg/body, respectively. After cycle 1, patients who were eligible and willing to continue vaccination proceeded to the extended treatment period. No DLT occurred in cycle 1 and no major safety problems were reported throughout the trial. One patient in cohort 2, three patients in cohort 3 and two patients in cohort 4 achieved stable disease. CTL and DTH responses following vaccination were also observed across the four cohorts. OCV‐C02 at 0.3 to 6 mg/body was found to be safe and well tolerated. Trial registrations: JAPIC clinical trials registry (ID: JapicCTI‐132075) and ClinicalTrials.Gov (ID: NCT01801930).

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Phase 1 study of OCV‐C02, a peptide vaccine consisting of two peptide epitopes for refractory metastatic colorectal cancer

et al. 2017

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“…Computational and “-omics” approaches to identify and validate immunostimulatory antigens and epitopes are critical for both cancer and infectious disease vaccine design (47, 48). Applications of these approaches to infectious disease challenges, such as creating a universal vaccine for influenza, have shown promising results (49).…”

Section: Introductionmentioning

confidence: 99%

Listening to each other: Infectious disease and cancer immunology

et al. 2017

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Epitopes

Kirpach

2015

Encyclopedia of Life Sciences

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T and B lymphocytes, the mediators of adaptive immune responses, express antigen‐specific receptors that allow them to discriminate between self and a virtually unlimited number of nonself molecules. Their receptors specifically recognise and bind subdomains of foreign macromolecules which are called epitopes. T‐cell epitopes (TCEs) and B‐cell epitopes (BCEs) differ fundamentally in the way they are recognised by the immune system. BCEs are recognised as three‐dimensional structures on the surface of native antigens. TCEs are parts of internalised and processed antigens that are presented to T lymphocytes in association with molecules of the major histocompatibility complex. As in a biological system T‐ and B‐cell receptors or antibody molecules face a virtual infinite number of structures, cognate interactions with epitopes are the basis of the primordial intelligence that drives the teleological choices of the immune system. Immunodominance directs the immune response towards selected epitopes. Key Concepts Surface immunoglobulins of B cells and antibodies recognise the B‐cell epitope (BCE) of an antigen in its native conformation, while T‐cell receptors (TCRs) recognise the T‐cell epitopes (TCEs) only after intracellular processing of the antigen, and in association with major histocompatibility complex (MHC) molecules. The main common feature of B‐cell epitopes is accessibility on the surface of the antigen. TCE peptides that bind to the same allele of MHC molecules share common ‘anchor’ residues (motifs) that contact the MHC molecule. TCEs presented by MHC class II molecules are longer and more variable in size and their anchor residues are less well defined than those of peptides presented by MHC class I molecules. Patterns of anchor residues facilitate the prediction of peptide binding to MHC molecules. The TCR–MHC–peptide tripartite cognate interaction in concert with coreceptors and other signalling modules mediate T‐cell activation. Immunodominance refers to the concept that only a small subset of the potential epitopes (TCEs or BCEs) present in a given antigen elicit an immune response. Mimotopes are small molecules that mimic the structure of complex conformational epitopes without any sequence homology. While TCEs can be predicted with some confidence, ill‐defined characteristic features of BCEs limit their predictability. Epitope‐based vaccines will allow to better manage desired and undesired cross‐reactivity.

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Advances in the study of HLA-restricted epitope vaccines

Cited by 47 publications

References 94 publications

Phase 1 study of OCV‐C02, a peptide vaccine consisting of two peptide epitopes for refractory metastatic colorectal cancer

Phase 1 study of OCV‐C02, a peptide vaccine consisting of two peptide epitopes for refractory metastatic colorectal cancer

Listening to each other: Infectious disease and cancer immunology

Epitopes

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