Biology subjects

Jafar, U.

Publications and source records attributed to Jafar, U..

2 recordsLinked to original sources

bioRxiv2025

Anti-tumor effects of a novel cell penetrating peptide-based therapeutic approach to target Lactate Dehydrogenase C (LDHC) in triple negative breast cancer.

BackgroundLactate Dehydrogenase C (LDHC) is a promising candidate for therapeutic targeting thanks to its highly tumor-specific expression, immunogenicity, and pro-tumorigenic functions. Aberrant LDHC expression is associated with poor clinical outcomes in multiple cancers, including breast cancer. However, no specific LDHC inhibitors are currently available, highlighting the need for novel strategies to selectively target LDHC in tumor cells. This study explores the anti-tumor potential of cell-penetrating peptides (CPPs) to target LDHC in triple negative breast cancer (TNBC). MethodsFour CPPs were evaluated for their ability to deliver LDHC siRNA to tumor cells, including the positively charged 10R peptide (10R) and three bifunctional peptides containing the integrin v{beta}3 recognition motif Arg-Gly-Asp (RGD): 10R-RGD, cyclicRGD-10R (cRGD-10R), and internalizing RGD-10R (iRGD-10R). We characterized the physicochemical properties of all CPP:siRNA complexes, and determined their serum stability, cytotoxicity, cellular uptake, and LDHC silencing efficiency in vitro. The anti-tumor effects and cytotoxicity of cRGD-10R:siRNA and iRGD-10R:siRNA complexes were further assessed in a TNBC xenograft zebrafish model. ResultsAll four CPPs formed stable nanocomplexes with favorable safety profiles. The 10R-RGD and cRGD-10R peptides demonstrated the most efficient LDHC knockdown, reduced the clonogenic ability of TNBC cells and enhanced their treatment response to the chemotherapeutic drug olaparib in vitro. Treatment of TNBC xenograft zebrafish with 10R-RGD:siRNA and cRGD-10R:siRNA complexes significantly reduced tumor burden without inducing major toxicity. Conclusion Our findings demonstrate that CPP-based siRNA delivery provides a novel and safe approach to target LDHC, either as a monotherapy or in combination with common anti-cancer drugs, to enhance treatment outcomes.

cancer biology↗

bioRxiv2024

Longitudinal cellular and humoral immune responses following Covid-19 BNT162b2-mRNA-based booster vaccination of craft and manual workers in Qatar.

IntroductionIn March 2020, the rapid spread of SARS-CoV-2 prompted global vaccination campaigns to mitigate COVID-19 disease severity and mortality. The 2-dose BNT162b2- mRNA vaccine effectively reduced infection and mortality rates, however, waning vaccine effectiveness necessitated the introduction of a third vaccine dose or booster. To assess the magnitude and longevity of booster-induced immunity, we conducted a longitudinal study of SARS-CoV-2 specific cellular and humoral immune responses among Qatars vulnerable craft and manual worker community. We also investigated the impact of prior naturally acquired immunity on booster vaccination efficacy. MethodsSeventy healthy participants were enrolled in the study, of whom half had prior SARS-CoV-2 infection. Blood samples were collected before and after booster vaccination to evaluate immune responses through SARS- CoV-2 specific ELISpots, IgG ELISA, neutralization assays, and flow cytometric immunophenotyping ResultsT cell analysis revealed increased Th1 cellular responses, marked by enhanced IFN-{gamma} release, in recently infected participants, which was further enhanced by booster vaccination for up to 6-months. Furthermore, booster vaccination stimulated cytotoxic T cell responses in infection-naive participants, characterized by granzyme B production. Both natural SARS-CoV-2 infection and booster vaccination induced robust and durable SARS-CoV-2 specific humoral immune responses, with high neutralizing antibody levels. Prior natural infection was also linked to an increased number of class- switched B cells prior to booster vaccination. ConclusionThese findings underscore the importance of booster vaccination in enhancing anti-viral immunity across both infection-naive and previously infected individuals, enhancing distinct arms of the anti-viral immune response and prolonging naturally acquired immunity.

immunology↗