Pathogens: Our Allies against Cancer?

Buonaguro, Luigi; Cerullo, Vincenzo

doi:10.1016/j.ymthe.2020.12.005

Cited by 12 publications

(11 citation statements)

References 15 publications

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“…Different research groups have reported that patients with cancer with tumor lesions expressing tumor antigens with high similarity to pathogens may have a better clinical outcome. [32][33][34][35][36] We have recently shown that mutated neoantigens may show >50% sequence similarity to PaAs and the central TCR-facing residues can be identical. Paired neoantigens and PaAs were shown to elicit cross-reacting T cells in immunized mice and to be cross-recognized by peripheral blood mononuclear cells (PBMC) from a long-term surviving patient with hepatocellular carcinoma (HCC).…”

Section: Introductionmentioning

confidence: 99%

Identification and validation of viral antigens sharing sequence and structural homology with tumor-associated antigens (TAAs).

Ragone

Manolio

Cavalluzzo

et al. 2021

J Immunother Cancer

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BackgroundThe host’s immune system develops in equilibrium with both cellular self-antigens and non-self-antigens derived from microorganisms which enter the body during lifetime. In addition, during the years, a tumor may arise presenting to the immune system an additional pool of non-self-antigens, namely tumor antigens (tumor-associated antigens, TAAs; tumor-specific antigens, TSAs).MethodsIn the present study, we looked for homology between published TAAs and non-self-viral-derived epitopes. Bioinformatics analyses and ex vivo immunological validations have been performed.ResultsSurprisingly, several of such homologies have been found. Moreover, structural similarities between paired TAAs and viral peptides as well as comparable patterns of contact with HLA and T cell receptor (TCR) α and β chains have been observed. Therefore, the two classes of non-self-antigens (viral antigens and tumor antigens) may converge, eliciting cross-reacting CD8+ T cell responses which possibly drive the fate of cancer development and progression.ConclusionsAn established antiviral T cell memory may turn out to be an anticancer T cell memory, able to control the growth of a cancer developed during the lifetime if the expressed TAA is similar to the viral epitope. This may ultimately represent a relevant selective advantage for patients with cancer and may lead to a novel preventive anticancer vaccine strategy.

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Section: Introductionmentioning

confidence: 99%

Identification and validation of viral antigens sharing sequence and structural homology with tumor-associated antigens (TAAs).

Ragone

Manolio

Cavalluzzo

et al. 2021

J Immunother Cancer

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“…Homology analysis was performed to identify homology with viral epitopes, given that we have recently shown that such homology could represent a selective advantage in controlling tumor establishment and progression. Indeed, memory T cells induced by a previous viral infection could be promptly recalled to expand by tumor antigens, showing high homology with the viral antigens [ 28 , 29 ]. Out of the 28 SBs, 5 showed homology with viral epitope sequences including influenza virus, hepatitis C virus (HCV), hepatitis B virus (HBV), adenovirus, human cytomegalovirus (HCMV), and human calicivirus.…”

Section: Discussionmentioning

confidence: 99%

Novel Molecular Targets for Hepatocellular Carcinoma

Cavalluzzo

Mauriello

Ragone

et al. 2021

Cancers

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Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer globally. Indeed, only a few treatments are available, most of which are effective only for the early stages of the disease. Therefore, there is an urgent needing for potential markers for a specifically targeted therapy. Candidate proteins were selected from datasets of The Human Protein Atlas, in order to identify specific tumor-associated proteins overexpressed in HCC samples associated with poor prognosis. Potential epitopes were predicted from such proteins, and homology with peptides derived from viral proteins was assessed. A multiparametric validation was performed, including recognition by PBMCs from HCC-patients and healthy donors, showing a T-cell cross-reactivity with paired epitopes. These results provide novel HCC-specific tumor-associated antigens (TAAs) for immunotherapeutic anti-HCC strategies potentially able to expand pre-existing virus-specific CD8+ T cells with superior anticancer efficacy.

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“…Previous studies succeeded in producing the chimeric parvovirus AAV2/B19, in which parvovirus B19 capsid was used to pseudopackage the AAV2 genome ( Ponnazhagan et al, 1998 ). However, the cross genera packaging efficiency remained poor, and the rAAV2/B19 vector is not practically employed in gene therapy ( Fakhiri and Grimm, 2021 ). The rAAV2 genome can also be packaged by the HBoV1 capsid to assemble a chimeric parvoviral vector, rAAV2/HBoV1.…”

Section: Hbov1 Capsid-based Raav Vectorsmentioning

confidence: 99%

Recent Advances in Molecular Biology of Human Bocavirus 1 and Its Applications

et al. 2021

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Human bocavirus 1 (HBoV1) was discovered in human nasopharyngeal specimens in 2005. It is an autonomous human parvovirus and causes acute respiratory tract infections in young children. HBoV1 infects well differentiated or polarized human airway epithelial cells in vitro. Unique among all parvoviruses, HBoV1 expresses 6 non-structural proteins, NS1, NS1-70, NS2, NS3, NS4, and NP1, and a viral non-coding RNA (BocaSR), and three structural proteins VP1, VP2, and VP3. The BocaSR is the first identified RNA polymerase III (Pol III) transcribed viral non-coding RNA in small DNA viruses. It plays an important role in regulation of viral gene expression and a direct role in viral DNA replication in the nucleus. HBoV1 genome replication in the polarized/non-dividing airway epithelial cells depends on the DNA damage and DNA repair pathways and involves error-free Y-family DNA repair DNA polymerase (Pol) η and Pol κ. Importantly, HBoV1 is a helper virus for the replication of dependoparvovirus, adeno-associated virus (AAV), in polarized human airway epithelial cells, and HBoV1 gene products support wild-type AAV replication and recombinant AAV (rAAV) production in human embryonic kidney (HEK) 293 cells. More importantly, the HBoV1 capsid is able to pseudopackage an rAAV2 or rHBoV1 genome, producing the rAAV2/HBoV1 or rHBoV1 vector. The HBoV1 capsid based rAAV vector has a high tropism for human airway epithelia. A deeper understanding in HBoV1 replication and gene expression will help find a better way to produce the rAAV vector and to increase the efficacy of gene delivery using the rAAV2/HBoV1 or rHBoV1 vector, in particular, to human airways. This review summarizes the recent advances in gene expression and replication of HBoV1, as well as the use of HBoV1 as a parvoviral vector for gene delivery.

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Pathogens: Our Allies against Cancer?

Cited by 12 publications

References 15 publications

Identification and validation of viral antigens sharing sequence and structural homology with tumor-associated antigens (TAAs).

Identification and validation of viral antigens sharing sequence and structural homology with tumor-associated antigens (TAAs).

Novel Molecular Targets for Hepatocellular Carcinoma

Recent Advances in Molecular Biology of Human Bocavirus 1 and Its Applications

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