Generation of multiepitope cancer vaccines based on large combinatorial libraries of survivin‐derived mutant epitopes

Domínguez-Romero, Allan Noé; Martínez-Cortés, Fernando; Munguı́a, Maria Elena; Odales, Josué; Gevorkian, Goar; Manoutcharian, Karen

doi:10.1111/imm.13233

Cited by 15 publications

(10 citation statements)

References 39 publications

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“…Multiepitope cancer vaccines prepared against BIRC5 in recent years inhibit tumor growth and strongly suppress lung metastasis. We demonstrated that the vaccine-induced broad cellular immune responses, accompanied by T cell infiltration 29 . Several studies have shown that vaccines targeting BIRC5 have promising anti-tumor effects through different approaches.…”

Section: Discussionmentioning

confidence: 90%

BIRC5 is a prognostic biomarker associated with tumor immune cell infiltration

Xiao

et al. 2021

Sci Rep

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BIRC5 is an immune-related gene that inhibits apoptosis and promotes cell proliferation. It is highly expressed in most tumors and leads to poor prognosis in cancer patients. This study aimed to analyze the relationship between the expression level of BIRC5 in different tumors and patient prognosis, clinical parameters, and its role in tumor immunity. Genes co-expressed with BIRC5 were analyzed, and functional enrichment analysis was performed. The relationship between BIRC5 expression and the immune and stromal scores of tumors in pan-cancer patients and the infiltration level of 22 tumor-infiltrating lymphocytes (TILs) was analyzed. The correlation of BIRC5 with immune checkpoints was conducted. Functional enrichment analysis showed that genes co-expressed with BIRC5 were significantly associated with the mitotic cell cycle, APC/C-mediated degradation of cell cycle proteins, mitotic metaphase, and anaphase pathways. Besides, the high expression of BIRC5 was significantly correlated with the expression levels of various DNA methyltransferases, indicating that BIRC5 regulates DNA methylation. We also found that BIRC5 was significantly correlated with multiple immune cells infiltrates in a variety of tumors. This study lays the foundation for future research on how BIRC5 modulates tumor immune cells, which may lead to the development of more effective targeted tumor immunotherapies.

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Section: Discussionmentioning

confidence: 90%

BIRC5 is a prognostic biomarker associated with tumor immune cell infiltration

Xiao

et al. 2021

Sci Rep

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“…Several tumour-associated antigens (TAAs) have been identified as promising targets for cancer immunotherapy, including mucin-1 (MUC1) [ 10 ] and survivin [ 11 , 12 , 13 ]. MUC1 is a transmembrane glycoprotein that is overexpressed in approximately 90% of BCs.…”

Section: Introductionmentioning

confidence: 99%

Delivering Two Tumour Antigens Survivin and Mucin-1 on Virus-Like Particles Enhances Anti-Tumour Immune Responses

et al. 2021

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Breast cancer (BC) is the most frequently diagnosed cancer in women, with many patients experiencing recurrence following treatment. Antigens delivered on virus-like particles (VLPs) induce a targeted immune response and here we investigated whether the co-delivery of multiple antigens could induce a superior anti-cancer response for BC immunotherapy. VLPs were designed to recombinantly express murine survivin and conjugated with an aberrantly glycosylated mucin-1 (MUC1) peptide using an intracellular cleavable bis-arylhydrazone linker. Western blotting, electron microscopy and UV absorption confirmed survivin-VLP expression and MUC1 conjugation. To assess the therapeutic efficacy of VLPs, orthotopic BC tumours were established by injecting C57mg.MUC1 cells into the mammary fat pad of mice, which were then vaccinated with surv.VLP-SS-MUC1 or VLP controls. While wild-type mice vaccinated with surv.VLP-SS-MUC1 showed enhanced survival compared to VLPs delivering either antigen alone, MUC1 transgenic mice vaccinated with surv.VLP-SS-MUC1 showed no enhanced survival compared to controls. Hence, while co-delivery of two tumour antigens on VLPs can induce a superior anti-tumour immune response compared to the delivery of single antigens, additional strategies must be employed to break tolerance when targeted tumour antigens are expressed as endogenous self-proteins. Using VLPs for the delivery of multiple antigens represents a promising approach to improving BC immunotherapy, and has the potential to be an integral part of combination therapy in the future.

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“…Importantly, the simultaneous presentation of a large number of epitope variants by immunization with VEL vaccines may recall responses of the past, induce responses against antigens present during immunization, and induce T cells capable of recognizing future mutated antigens, thus reducing the chances of immune escape: in this manner, VEL immunogens are in a class all their own. They are capable of inducing the largest possible repertoire of both B and T cells, and we demonstrated their ability to induce HIV-1 broadly neutralizing sera in mice (half of Tier 2 HIV-1 isolates were neutralized; Charles-Niño et al 2011 ), and inhibit tumor growth and metastasis in an aggressive triple-negative breast cancer model (Domínguez-Romero et al 2020 ; Servín-Blanco et al 2018 ).…”

Section: Dynamic Immunogens Against Cancer and Beyond: Variable Epitope Librariesmentioning

confidence: 75%

“…The possible involvement of OAS, a strictly pathogen-related phenomenon, unappreciated in cancer immunology, might contribute to the final outcome of tumor-immune interactions. To elucidate our hypothesis that OAS may have a detrimental role in cancer evolution and immune escape (Domínguez-Romero et al 2020 ), we have generated preliminary experimental data (currently still in process), which highly suggests the presence of this phenomenon in cancer.…”

Section: Original Antigenic Sin In Avps and Cancermentioning

confidence: 99%

Neoantigen Cancer Vaccines: Real Opportunity or Another Illusion?

Manoutcharian

Valle

Gevorkian

2021

Arch. Immunol. Ther. Exp.

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In this communication, we will analyze some important factors and immunological phenomena related to neoantigen cancer vaccines, with particular emphasis on recently published Phase I clinical trials. Several obstacles and issues are addressed that challenge the current paradigm and inquire if neoantigens, which are essentially single-use vaccine candidates, are legitimate targets to induce protective immune responses with regard to the evolving mutational landscape. We also share insights into the striking similarities between cancer and antigenically variable pathogens and suggest that any successful vaccine against either should demonstrate a similar property: efficient induction of a diverse pool of immune cells equipped to prevent immune escape. Hence, to confront antigenic variability directly, we have employed our innovative vaccine concept, Variable Epitope Libraries, composed of large combinatorial libraries of heavily mutated epitopes, as a “universal” vaccine platform. Collectively, we offer critical analyses on key issues, which ultimately reflect on the prospective clinical relevance of personalized neoantigen vaccines which is still undefined.

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Generation of multiepitope cancer vaccines based on large combinatorial libraries of survivin‐derived mutant epitopes

Cited by 15 publications

References 39 publications

BIRC5 is a prognostic biomarker associated with tumor immune cell infiltration

BIRC5 is a prognostic biomarker associated with tumor immune cell infiltration

Delivering Two Tumour Antigens Survivin and Mucin-1 on Virus-Like Particles Enhances Anti-Tumour Immune Responses

Neoantigen Cancer Vaccines: Real Opportunity or Another Illusion?

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