Identification of a novel PD-L1 positive solid tumor transplantable in HLA-A*0201/DRB1*0101 transgenic mice

Rangan, Laurie; Galaine, Jeanne; Boidot, Romain; Hamieh, Mohamad; Dosset, Magalie; Francoual, Julie; Beziaud, Laurent; Pallandre, Jean-René; Joseph, Elodie Lauret Marie; Asgarova, Afag; Borg, Christophe; Saati, Talal Al; Godet, Yann; Latouche, Jean-Baptiste; Valmary‐Degano, Séverine; Adotévi, Olivier

doi:10.18632/oncotarget.16900

Cited by 4 publications

(3 citation statements)

References 35 publications

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“…O. Adotevi). The Sarc-A2 tumor cell line derives from a spontaneous arising sarcoma in HLA-A2/DR1 mice that was further transfected with the HLA-A2 molecules ( 32 ). To accurately evaluate the response directed against the human SVX peptides, all these tumor cell lines (expressing endogeneous murine survivin), were transfected after electroporation with a plasmid containing the whole human survivin sequence [pcDNA3-hsurvivin (pBir5 + )] ( 30 ).…”

Section: Methodsmentioning

confidence: 99%

High Therapeutic Efficacy of a New Survivin LSP-Cancer Vaccine Containing CD4+ and CD8+ T-Cell Epitopes

et al. 2018

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The efficacy of an antitumoral vaccine relies both on the choice of the antigen targeted and on its design. The tumor antigen survivin is an attractive target to develop therapeutic cancer vaccines because of its restricted over-expression and vital functions in most human tumors. Accordingly, several clinical trials targeting survivin in various cancer indications have been conducted. Most of them relied on short peptide-based vaccines and showed promising, but limited clinical results. In this study, we investigated the immunogenicity and therapeutic efficacy of a new long synthetic peptide (LSP)-based cancer vaccine targeting the tumor antigen survivin (SVX). This SVX vaccine is composed of three long synthetic peptides containing several CD4+ and CD8+ T-cell epitopes, which bind to various HLA class II and class I molecules. Studies in healthy individuals showed CD4+ and CD8+ T-cell immunogenicity of SVX peptides in human, irrespective of the individual's HLA types. Importantly, high frequencies of spontaneous T-cell precursors specific to SVX peptides were also detected in the blood of various cancer patients, demonstrating the absence of tolerance against these peptides. We then demonstrated SVX vaccine's high therapeutic efficacy against four different established murine tumor models, associated with its capacity to generate both specific cytotoxic CD8+ and multifunctional Th1 CD4+ T-cell responses. When tumors were eradicated, generated memory T-cell responses protected against rechallenge allowing long-term protection against relapses. Treatment with SVX vaccine was also found to reshape the tumor microenvironment by increasing the tumor infiltration of both CD4+ and CD8+ T cells but not Treg cells therefore tipping the balance toward a highly efficient immune response. These results highlight that this LSP-based SVX vaccine appears as a promising cancer vaccine and warrants its further clinical development.

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Section: Methodsmentioning

confidence: 99%

High Therapeutic Efficacy of a New Survivin LSP-Cancer Vaccine Containing CD4+ and CD8+ T-Cell Epitopes

et al. 2018

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“…According to the high frequency of these HLA alleles in the world population, this mouse model gained considerable interest in the field of tumor immunology and it has been used as preclinical tool for the evaluation of antitumor immunotherapies. Interestingly, both HLA-A*0201 and PD-L1 expressions increased on SARC-L1 after IFN-γ exposure in vitro defining this tumor very sensitive to several drugs commonly used to treat sarcoma and susceptible to anti-PD-L1 mAb therapy in vivo [ 222 ]. As we have described above, tumor cells might also express tsHLA-II molecules [ 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 ].…”

Section: Role Of Hla As a Predictive Biomarker For Ici-based Immunmentioning

confidence: 99%

Role of Human Leukocyte Antigen System as A Predictive Biomarker for Checkpoint-Based Immunotherapy in Cancer Patients

Sabbatino

Liguori

Polcaro

et al. 2020

IJMS

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Recent advances in cancer immunotherapy have clearly shown that checkpoint-based immunotherapy is effective in a small subgroup of cancer patients. However, no effective predictive biomarker has been identified so far. The major histocompatibility complex, better known in humans as human leukocyte antigen (HLA), is a very polymorphic gene complex consisting of more than 200 genes. It has a crucial role in activating an appropriate host immune response against pathogens and tumor cells by discriminating self and non-self peptides. Several lines of evidence have shown that down-regulation of expression of HLA class I antigen derived peptide complexes by cancer cells is a mechanism of tumor immune escape and is often associated to poor prognosis in cancer patients. In addition, it has also been shown that HLA class I and II antigen expression, as well as defects in the antigen processing machinery complex, may predict tumor responses in cancer immunotherapy. Nevertheless, the role of HLA in predicting tumor responses to checkpoint-based immunotherapy is still debated. In this review, firstly, we will describe the structure and function of the HLA system. Secondly, we will summarize the HLA defects and their clinical significance in cancer patients. Thirdly, we will review the potential role of the HLA as a predictive biomarker for checkpoint-based immunotherapy in cancer patients. Lastly, we will discuss the potential strategies that may restore HLA function to implement novel therapeutic strategies in cancer patients.

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“…T2 cells were cultured in Iscove's Modified Dulbecco's medium (IMDM) complete medium, according to the manufacturer's protocol. The sarcoma tumor cell line (SARC-A2) was derived from a spontaneously arising sarcoma in HLA-A2/DR1 mice (14). SARC-A2 cells were transduced with a lentiviral vector encoding GFP only (SARC-A2-GFP) or carrying the CD20 full human gene upstream of an IRES element followed by a GFP cassette (SARC-A2-hCD20-GFP).…”

Section: Cell Lines and Culturementioning

confidence: 99%

A Mimicry-Based Strategy Between Human and Commensal Antigens for the Development of a New Family of Immune Therapies for Cancer

Talpin,

Maia,

Carpier

et al. 2024

Preprint

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Peptide vaccines have emerged as a promising strategy for cancer immunotherapy, yet often lack of strong, specific and sustained immune responses against tumor antigens. To achieve a robust immune response, the effective selection of tumour antigens is crucial. While neoantigens trigger potent immune responses, their use suffers from patient specificity and their rarity in low-mutational tumors. Alternatively, the immunogenic potential of tumor-associated antigens (TAAs) is limited by central immune tolerance. Molecular mimicry and T cell cross-reactivity is a proposed mechanism to trigger a robust T cell-mediated antitumor response. Although molecular mimicry between pathogens and tumor antigens has been described, the potential benefits of exploiting this molecular mimicry with commensal bacterial antigens in antitumor immunity have not been thoroughly investigated despite strong evidence that the composition of the human microbiota significantly influences immune competency. Our new approach called OncoMimics™, which uses molecular mimicry between commensal bacterial and tumoral antigens to induce cross-reactive cytotoxic T cells against tumor cells. In preclinical studies, vaccination with OncoMimic™ peptides (OMPs) led to the expansion of CD8+T cells reacting against homologous tumor-associated antigen peptides and elicits cytotoxic activity against tumor cells. OMPs are efficiently recognized by a prevalent T cell population within the peripheral blood mononuclear cells of healthy individuals. An ongoing clinical trial (NCT04116658) using OncoMimics™ in patients with glioblastoma demonstrates early, durable, and cross-reactive tumor antigen CD8+T cell responses with pronounced memory persistence. By overcoming the current vaccine limitations, OncoMimics™ constitutes a promising strategy for enhancing cancer immunity and improving patient outcomes.Statement of SignificanceThis study introduces OncoMimics™, a peptide-based immunotherapy leveraging molecular mimicry to induce robust, cross-reactive T cell responses against tumor antigens, showing promising early results in an ongoing glioblastoma clinical trial (NCT04116658)

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Identification of a novel PD-L1 positive solid tumor transplantable in HLA-A0201/DRB10101 transgenic mice

Cited by 4 publications

References 35 publications

High Therapeutic Efficacy of a New Survivin LSP-Cancer Vaccine Containing CD4+ and CD8+ T-Cell Epitopes

High Therapeutic Efficacy of a New Survivin LSP-Cancer Vaccine Containing CD4+ and CD8+ T-Cell Epitopes

Role of Human Leukocyte Antigen System as A Predictive Biomarker for Checkpoint-Based Immunotherapy in Cancer Patients

A Mimicry-Based Strategy Between Human and Commensal Antigens for the Development of a New Family of Immune Therapies for Cancer

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