Adenovirus based virus-like-vaccines targeting endogenous retroviruses can eliminate growing colorectal cancers in mice

Neukirch, Lasse; Nielsen, Tea Kirkegaard; Laursen, Henriette; Daradoumis, Joana; Thirion, Christian; Holst, Peter Johannes

doi:10.18632/oncotarget.26680

Cited by 18 publications

(37 citation statements)

References 52 publications

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“…All these events lead to the generation of a novel pool of tumor-specific antigens identified in different tumor types that can be exploited as T cell targets on tumor cells [ 62 ]. HERV-derived antigens have been used to develop cancer vaccines and chimeric antigen receptor (CAR)-expressing T cells, which have been tested only in a pre-clinical setting to date [ 71 , 72 , 73 , 74 , 75 , 76 ]. Altogether, these pre-clinical studies show the safety, immunogenicity, and preliminary efficacy data, but none of these strategies have been tested in human clinical trials so far.…”

Section: Tumor Antigensmentioning

confidence: 99%

Selecting Target Antigens for Cancer Vaccine Development

Buonaguro

Tagliamonte

2020

Vaccines

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One of the principal goals of cancer immunotherapy is the development of efficient therapeutic cancer vaccines that are able to elicit an effector as well as memory T cell response specific to tumor antigens. In recent years, the attention has been focused on the personalization of cancer vaccines. However, the efficacy of therapeutic cancer vaccines is still disappointing despite the large number of vaccine strategies targeting different tumors that have been evaluated in recent years. While the preclinical data have frequently shown encouraging results, clinical trials have not provided satisfactory data to date. The main reason for such failures is the complexity of identifying specific target tumor antigens that should be unique or overexpressed only by the tumor cells compared to normal cells. Most of the tumor antigens included in cancer vaccines are non-mutated overexpressed self-antigens, eliciting mainly T cells with low-affinity T cell receptors (TCR) unable to mediate an effective anti-tumor response. In this review, the target tumor antigens employed in recent years in the development of therapeutic cancer vaccine strategies are described, along with potential new classes of tumor antigens such as the human endogenous retroviral elements (HERVs), unconventional antigens, and/or heteroclitic peptides.

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Section: Tumor Antigensmentioning

confidence: 99%

Selecting Target Antigens for Cancer Vaccine Development

Buonaguro

Tagliamonte

2020

Vaccines

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“…These vaccines were highly effective at managing to target growing colorectal carcinomas and eliminating small tumours in mice. Unlike targeting with invariant chains, using neoantigens where T-cells were the only adaptive mediators of tumour resistance, it was observed that the effect of therapy was dependent on both CD4 + and CD8 + T-cells combined [ 116 , 117 ]. Following the success in murine ERV, we are currently taking this concept forward targeting human ERVs.…”

Section: Adenovirus As Therapeutic Cancer Vaccines With Ervs As Tamentioning

confidence: 99%

Cancer Associated Endogenous Retroviruses: Ideal Immune Targets for Adenovirus-Based Immunotherapy

Bermejo

Ragonnaud

Daradoumis

et al. 2020

IJMS

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Cancer is a major challenge in our societies, according to the World Health Organization (WHO) about 1/6 deaths were cancer related in 2018 and it is considered the second leading cause of death globally. Immunotherapies have changed the paradigm of oncologic treatment for several cancers where the field had fallen short in providing competent therapies. Despite the improvement, broadly acting and highly effective therapies capable of eliminating or preventing human cancers with insufficient mutated antigens are still missing. Adenoviral vector-based vaccines are a successful tool in the treatment of various diseases including cancer; however, their success has been limited. In this review we discuss the potential of adenovirus as therapeutic tools and the current developments to use them against cancer. More specifically, we examine how to use them to target endogenous retroviruses (ERVs). ERVs, comprising 8% of the human genome, have been detected in several cancers, while they remain silent in healthy tissues. Their low immunogenicity together with their immunosuppressive capacity aid cancer to escape immunosurveillance. In that regard, virus-like-vaccine (VLV) technology, combining adenoviral vectors and virus-like-particles (VLPs), can be ideal to target ERVs and elicit B-cell responses, as well as CD8+ and CD4+ T-cells responses.

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“…This group manifested an analogous study with HERV-K(HML2) Gag protein as the promising target to elicit a long-lived T cell response against tumor in the murine model [86]. A similar strategy has also been employed through adenovirus-mediated delivery of murine melanoma-associated retrovirus (MelARV) proteins Gag and Env to form virus-like particles displaying the cancer-associated MelARV Env to the immune system in mice, which could stimulate T cell response to inhibit murine colorectal tumor growth [87]. Likewise, another group investigated the extent of vaccination protection in rhesus macaques against ERVs as means to target HIV-and cancer-associated endogenous retrotransposable elements.…”

Section: Immunotherapeutic Strategies Targeting Herv For Cancer Treatmentioning

confidence: 99%

Contribution of Human Retroviruses to Disease Development—A Focus on the HIV– and HERV–Cancer Relationships and Treatment Strategies

Grandi

Palanivelu

Lin

2020

Viruses

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Animal retroviruses are known for their transforming potential, and this is also true for the ones hosted by humans, which have gathered expanding attention as one of the potent causative agents in various disease, including specific cancer types. For instance, Human T Lymphotropic virus (HTLV) is a well-studied class of oncoviruses causing T cell leukemia, while human immunodeficiency virus (HIV) leads to acquired immunodeficiency syndrome (AIDS), which is linked to a series of defining cancers including Kaposi sarcoma, certain types of non-Hodgkin lymphoma, and cervical cancer. Of note, in addition to these “modern” exogenous retroviruses, our genome harbors a staggering number of human endogenous retroviruses (HERVs). HERVs are the genetic remnants of ancient retroviral germline infection of human ancestors and are typically silenced in normal tissues due to inactivating mutations and sequence loss. While some HERV elements have been appropriated and contribute to human physiological functions, others can be reactivated through epigenetic dysregulations to express retroviral elements and promote carcinogenesis. Conversely, HERV replication intermediates or protein products can also serve as intrinsic pathogen-associated molecular patterns that cause the immune system to interpret it as an exogenous infection, thereby stimulating immune responses against tumors. As such, HERVs have also been targeted as a potential internal strategy to sensitize tumor cells for promising immunotherapies. In this review, we discuss the dynamic role of human retroviruses in cancer development, focusing on HIV and HERVs contribution. We also describe potential treatment strategies, including immunotherapeutic targeting of HERVs, inhibiting DNA methylation to expose HERV signatures, and the use of antiretroviral drugs against HIV and HERVs, which can be employed as prospective anti-cancer modalities.

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Adenovirus based virus-like-vaccines targeting endogenous retroviruses can eliminate growing colorectal cancers in mice

Cited by 18 publications

References 52 publications

Selecting Target Antigens for Cancer Vaccine Development

Selecting Target Antigens for Cancer Vaccine Development

Cancer Associated Endogenous Retroviruses: Ideal Immune Targets for Adenovirus-Based Immunotherapy

Contribution of Human Retroviruses to Disease Development—A Focus on the HIV– and HERV–Cancer Relationships and Treatment Strategies

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