Biology subjects

Panagioti, E.

Publications and source records attributed to Panagioti, E..

3 recordsLinked to original sources

bioRxiv2026

Preclinical evaluation of Brincidofovir in glioblastoma demonstrates improved long term-survival and cytomegalovirus-dependent and independent effects

Cytomegalovirus (CMV) has been implicated in glioblastoma (GBM) progression. Ongoing clinical trials are assessing therapeutic approaches targeting CMV in GBM but to date no new therapy has been approved outside the standard of care. Previous preclinical studies have highlighted the potential of the antiviral drug Cidofovir (CDV) in GBM; however, its clinical use is limited by dose-dependent nephrotoxicity and poor cellular uptake, necessitating high intravenous doses to achieve therapeutic activity. Brincidofovir (BCV), a lipid conjugate of CDV has been developed, which does not induce nephrotoxicity and has significantly greater cellular bioavailability. Here we examined the effects of BCV in a newly established CMV-driven GBM model (SB28) and in patient-derived tumor neurospheres. We show that BCV prolongs survival in vivo and exerts both CMV-dependent and independent antitumor effects. Mechanistically, BCV induces DNA damage and cell cycle dysregulation in GBM cells and inhibits proliferation of patient-derived neurospheres in a dose-dependent manner. These data identify BCV as a dual-action therapeutic that suppresses viral oncomodulation while directly targeting tumor cell viability.

cancer biology↗

bioRxiv2026

High-throughput epitope screening of the Human Cytomegalovirus immediate early protein 2 identifies promising antigenic T cell targets

Human Cytomegalovirus (HCMV) is an omnipresent pathogen that is associated with increased morbidity and mortality of immunocompromised individuals. Studies of T-cell immunity to HCMV primarily reflect anti-CMV pp65 or immediate early antigen 1 (IE-1) activity. Recent evidence highlights the importance of the major immediate-early 2 (IE2) protein, which is expressed early after HCMV infection and reactivation, for regulating the lytic HCMV replication cycle. In this study, we designed a comprehensive screening approach to assess T cell responses against the IE2 HCMV protein in the peripheral blood of 15 HCMV-seropositive and 6 HCMV-seronegative healthy adults using IE2 synthetic long peptide (SLP) pools and cytokine flow cytometry. The T cell response against the IE2 protein was dominated by CD4+ T cells whereas IE2-specific CD8+ T-cell reactivity was measured in only 3 donors. Most of the donors recognized chiefly the IE2351-434 residues, revealing a remarkably immunogenic area of the protein. Numerous novel HLA class I- and II-restricted IE2 T-cell epitopes were identified. Functional characterization of the IE2 CD4+ and CD8+ T cell responses uncovered 5 highly antigenic SLPs, which induced polyfunctional Th1 cytokine (IFN-{gamma}+/ TNF+/ IL-2+) response and could serve as candidate vaccine antigens. Evaluation of these 5 highly antigenic IE2 SLPs in T cell-inducing vaccines aiming to inhibit HCMV infection by targeting the expression of immediate-early genes is warranted.

immunology↗

bioRxiv2026

MAPKAP Kinase 2 Orchestrates Memory T Cell Inflation in Cytomegalovirus Infection

Memory T cell inflation is a distinctive immunological phenomenon observed during persistent viral infections, such as Cytomegalovirus (CMV). Unlike conventional memory T cell responses, which contract after infection resolution, a subset of CMV-specific T cells undergoes a progressive and sustained expansion, termed "inflation", which is thought to be critical for long-term immune surveillance. The molecular mechanisms that govern memory T cell inflation remain incompletely understood, yet they are pivotal for understanding immune persistence and designing strategies against chronic viral infections. In this study, we investigate the role of MAP kinase-activated protein kinase 2 (MK2), a key downstream effector of p38 MAPK signaling, in regulating T cell responses during murine CMV (MCMV) infection. Using MK2 knockout (MK2-KO) mice, we demonstrate that MK2 deficiency alters the dynamics of MCMV-specific CD8 T cell responses without impairing viral control or tissue replication. MK2 deficiency led to a reduction in non-inflationary MCMV-specific CD8 T cells during the acute phase, followed by enhanced expansion of inflationary CD8 T cell subsets during persistence. Furthermore, MK2-KO mice exhibited impaired effector differentiation, as evidenced by decreased expression of the terminal differentiation marker KLRG1 on MCMV-specific CD8 T cells. Collectively, these findings identify MK2 as a pivotal regulator of CD8 T cell magnitude, kinetics, and phenotype during both acute and chronic MCMV infection. By elucidating the role of MK2 in the regulation of memory T cell inflation, this study provides new mechanistic insight into immune regulation with implications for vaccination, chronic infection, and immune aging. Graphical abstractThe graphical abstract was created using BioRender (https://biorender.com/). O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/699974v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@140d602org.highwire.dtl.DTLVardef@1a23691org.highwire.dtl.DTLVardef@ac75b6org.highwire.dtl.DTLVardef@640d68_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗