Self-delivering RNAi immunotherapeutic PH-762 silences PD-1 to generate local and abscopal antitumor efficacy.

Objective: Immunotherapeutic inhibition of PD-1 by systemically administered monoclonal antibodies is widely used in cancer treatment, but it may cause severe immune-related adverse events (irSAEs). Neoadjuvant PD-1 inhibition before surgery has shown promise in reducing recurrence by stimulating durable antitumor immunity. Local intratumoral (IT) immunotherapy is a potential strategy to minimize irSAEs, but antibodies have limited tumor penetration, making them less suitable for this approach.

Oxidized high-density lipoprotein and low-density lipoprotein in adolescents with obesity and metabolic dysfunction-associated steatotic liver disease.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly common in the pediatric population and may increase risk for developing cardiovascular disease (CVD) in people with MASLD. Oxidized high-density lipoprotein (oxHDL) and oxidized low-density lipoprotein (oxLDL) are modified, pro-atherosclerotic lipoproteins that are increased in adults with MASLD and CVD but have not been reported in adolescents with MASLD.

Purpose: To determine if oxLDL and oxHDL are increased in adolescents with MASLD.

Increased trends in reported sexually transmitted infections according to age groups and sex in Spain, 2016-2022.

Objective: Our objective was to assess trends in three sexually transmitted infections (STIs) - gonorrhoea, chlamydia and syphilis - in Spain, by age group and sex from 2016 to 2022.

Study Design: Retrospective observational study.

Methods: Data from epidemiological surveillance system were used to calculate the incidence rate for each STIs by age group and sex.

INTASYL self-delivering RNAi decreases TIGIT expression, enhancing NK cell cytotoxicity: a potential application to increase the efficacy of NK adoptive cell therapy against cancer.

Natural killer (NK) cells are frontline defenders against cancer and are capable of recognizing and eliminating tumor cells without prior sensitization or antigen presentation. Due to their unique HLA mismatch tolerance, they are ideal for adoptive cell therapy (ACT) because of their ability to minimize graft-versus-host-disease risk. The therapeutic efficacy of NK cells is limited in part by inhibitory immune checkpoint receptors, which are upregulated upon interaction with cancer cells and the tumor microenvironment.