Cross-reactive CD8 T cell responses to tumor-associated antigens (TAAs) and homologous microbiota-derived antigens (MoAs).

Background: We have recently shown extensive sequence and conformational homology between tumor-associated antigens (TAAs) and antigens derived from microorganisms (MoAs). The present study aimed to assess the breadth of T-cell recognition specific to MoAs and the corresponding TAAs in healthy subjects (HS) and patients with cancer (CP).

Method: A library of > 100 peptide-MHC (pMHC) combinations was used to generate DNA-barcode labelled multimers.

Antigenic molecular mimicry in viral-mediated protection from cancer: the HIV case.

Background: People living with HIV/AIDS (PLWHA) show a reduced incidence for three cancer types, namely breast, prostate and colon cancers. In the present study, we assessed whether a molecular mimicry between HIV epitopes and tumor associated antigens and, consequently, a T cell cross-reactivity could provide an explanation for such an epidemiological evidence.

Methods: Homology between published TAAs and non-self HIV-derived epitopes have been assessed by BLAST homology.

Molecular mimicry between tumor associated antigens and microbiota-derived epitopes.

Background: The gut microbiota profile is unique for each individual and are composed by different bacteria species according to individual birth-to-infant transitions. In the last years, the local and systemic effects of microbiota on cancer onset, progression and response to treatments, such as immunotherapies, has been extensively described. Here we offer a new perspective, proposing a role for the microbiota based on the molecular mimicry of tumor associated antigens by microbiome-associated antigens.

Novel Molecular Targets for Hepatocellular Carcinoma.

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.

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

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.

MHC-Optimized Peptide Scaffold for Improved Antigen Presentation and Anti-Tumor Response.

Tumor Associated Antigens (TAAs) may suffer from an immunological tolerance due to expression on normal cells. In order to potentiate their immunogenicity, heteroclitic peptides (htcPep) were designed according to prediction algorithms. In particular, specific modifications were introduced in peptide residues facing to TCR.

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

Background: The 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).

Methods: In the present study, we looked for homology between published TAAs and non-self-viral-derived epitopes.

Human Endogenous Retrovirus Reactivation: Implications for Cancer Immunotherapy.

Human endogenous retroviruses (HERVs) derive from ancestral exogenous retroviruses whose genetic material has been integrated in our germline DNA. Several lines of evidence indicate that cancer immunotherapy may benefit from HERV reactivation, which can be induced either by drugs or by cellular changes occurring in tumor cells. Indeed, several studies indicate that HERV proviral DNA can be transcribed either to double-stranded RNA (dsRNA) that is sensed as a "danger signal" by pattern recognition receptors (PRRs), leading to a viral mimicry state, or to mRNA that is translated into proteins that may contribute to the landscape of tumor-specific antigens (TSAs).

Identification and characterization of heteroclitic peptides in TCR-binding positions with improved HLA-binding efficacy.

The antigenicity as well as the immunogenicity of tumor associated antigens (TAAs) may need to be potentiated in order to break the immunological tolerance. To this aim, heteroclitic peptides were designed introducing specific substitutions in the residue at position 4 (p4) binding to TCR. The effect of such modifications also on the affinity to the major histocompatibility class I (MHC-I) molecule was assessed.

Immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy.

Background: We have previously shown that HCC patients and healthy subjects are equally responsive to a RNAdjuvant, a novel TLR-7/8/RIG-I agonist based on noncoding RNA developed by CureVac, by an ex vivo evaluation. However, the immunological effect of adjuvants on immune cells from cancer patients undergoing chemotherapy remains to be demonstrated. Different adjuvants currently used in cancer vaccine clinical trials were evaluated in the present study on immune cells from cancer patients before and after chemotherapy in an ex vivo setting.

Tackling hepatocellular carcinoma with individual or combinatorial immunotherapy approaches.

Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer globally. Indeed, there is a single drug approved as first-line systemic therapy in advanced unresectable HCC, providing a very limited survival benefit. In earlier stages, 5-year survival rates after surgical and loco-regional therapies are extremely variable depending on the stage of disease.