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

Ragone, Concetta; Manolio, Carmen; Cavalluzzo, Beatrice; Mauriello, Angela; Tornesello, Maria Lina; Buonaguro, Franco M.; Castiglione, Filippo; Vitagliano, Luigi; Iaccarino, Emanuela; Ruvo, Menotti; Tagliamonte, Maria; Buonaguro, Luigi

doi:10.1136/jitc-2021-002694

Cited by 35 publications

(31 citation statements)

References 46 publications

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“…We have recently shown that TAAs may share high homology to viral antigens, suggesting an established antiviral memory T-cell immunity able to cross-react with tumor antigens [ 28 ]. Therefore, the predicted 28 SBs were further screened for homology to sequences derived from human viruses in BLAST, and several viral peptides were found.…”

Section: Resultsmentioning

confidence: 99%

“…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%

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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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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Novel Molecular Targets for Hepatocellular Carcinoma

Cavalluzzo

Mauriello

Ragone

et al. 2021

Cancers

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“…Viral infections elicit memory T-cells that may represent preventive anti-cancer vaccines. Homology between published tumor-associated antigens and non-self-viral-derived epitopes has been observed, with structural similarities between paired tumor-associated antigens and viral peptides as well as comparable patterns of contact with HLA and TCR α and β chains [ 96 ]. As such, viral antigens and tumor-associated antigens may elicit cross-reacting CD8 + T cell responses which could affect cancer progression.…”

Section: Drivers Of Immune Responsesmentioning

confidence: 99%

“…As such, viral antigens and tumor-associated antigens may elicit cross-reacting CD8 + T cell responses which could affect cancer progression. Previous exposure to specific viral epitopes may result in the establishment of a bispecific antiviral/anticancer T cell memory which may represent a relevant selective advantage for patients with cancer and provide a totally new set of antigens for developing a novel anticancer vaccine strategy [ 96 ].…”

Section: Drivers Of Immune Responsesmentioning

confidence: 99%

Perspectives in Immunotherapy: meeting report from the Immunotherapy Bridge, December 1st–2nd, 2021

et al. 2022

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Over the past decade, immunotherapy has become an increasingly fundamental modality in the treatment of cancer. The positive impact of immune checkpoint inhibition, especially anti-programmed death (PD)-1/PD-ligand (L)1 blockade, in patients with different cancers has focused attention on the potential for other immunotherapeutic approaches. These include inhibitors of additional immune checkpoints, adoptive cell transfer (ACT), and therapeutic vaccines. Patients with advanced cancers who previously had limited treatment options available may now benefit from immunotherapies that can offer durable responses and improved survival outcomes. However, despite this, a significant proportion of patients fail to respond to immunotherapy, especially those with less immunoresponsive cancer types, and there remains a need for new treatment strategies.The virtual Immunotherapy Bridge (December 1st–2nd, 2021), organized by the Fondazione Melanoma Onlus, Naples, Italy in collaboration with the Society for Immunotherapy of Cancer addressed several areas of current research in immunotherapy, including lessons learned from cell therapies, drivers of immune response, and trends in immunotherapy across different cancers, and these are summarised here.

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“…The improved prognosis in cancer patients bearing tumors expressing TuAs sharing sequence homology with viral antigens has been anecdotally reported in melanoma and pancreatic cancer [ 7 , 8 ]. Moreover, our group has shown very recently that several TAAs share sequence and structural homology with viral antigens [ 9 ] and that liver cancer cells presenting a mutated TSA mimicking the Vaccinia Virus (VV) antigen can be identified in a long-term survival patient with hepatocellular carcinoma (HCC) [ 10 ]. Finally, a decreased tumor growth and extended survival has been shown in a melanoma animal model presenting a TuA sharing sequence homology to a commensal’s antigen [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Long-term memory T cells as preventive anticancer immunity elicited by TuA-derived heteroclitic peptides

et al. 2021

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The host’s immune system may be primed against antigens during the lifetime (e.g. microorganisms antigens—MoAs), and swiftly recalled upon growth of a tumor expressing antigens similar in sequence and structure. C57BL/6 mice were immunized in a preventive setting with tumor antigens (TuAs) or corresponding heteroclitic peptides specific for TC-1 and B16 cell lines. Immediately or 2-months after the end of the vaccination protocol, animals were implanted with cell lines. The specific anti-vaccine immune response as well as tumor growth were regularly evaluated for 2 months post-implantation. The preventive vaccination with TuA or their heteroclitic peptides (hPep) was able to delay (B16) or completely suppress (TC-1) tumor growth when cancer cells were implanted immediately after the end of the vaccination. More importantly, TC-1 tumor growth was significantly delayed, and suppressed in 6/8 animals, also when cells were implanted 2-months after the end of the vaccination. The vaccine-specific T cell response provided a strong immune correlate to the pattern of tumor growth. A preventive immunization with heteroclitic peptides resembling a TuA is able to strongly delay or even suppress tumor growth in a mouse model. More importantly, the same effect is observed also when tumor cells are implanted 2 months after the end of vaccination, which corresponds to 8 – 10 years in human life. The observed potent tumor control indicates that a memory T cell immunity elicited during the lifetime by a antigens similar to a TuA, i.e. viral antigens, may ultimately represent a great advantage for cancer patients and may lead to a novel preventive anti-cancer vaccine strategy.

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

Cited by 35 publications

References 46 publications

Novel Molecular Targets for Hepatocellular Carcinoma

Novel Molecular Targets for Hepatocellular Carcinoma

Perspectives in Immunotherapy: meeting report from the Immunotherapy Bridge, December 1st–2nd, 2021

Long-term memory T cells as preventive anticancer immunity elicited by TuA-derived heteroclitic peptides

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