Int. J. Transl. Med., Volume 5, Issue 4 (December 2025) – 2 articles

Background/Objectives: Whilst adoptive cell therapy (ACT) using chimeric antigen receptor-engineered T (CAR-T) cells represents an efficient approach for the treatment of patients suffering from several hematological malignancies, solid tumors have been shown to be far more challenging to tackle, mainly due to the hostile tumor microenvironment that inhibits optimal T cell functionality. As proven by the broad clinical success of immune checkpoint inhibitors, blocking the interaction of programmed cell death ligand 1 (PD-L1) expressed on tumor cells and the checkpoint receptor programmed cell death 1 (PD-1) expressed on activated T cells allows an intrinsic T cell-mediated anti-tumor response to be unleashed. We developed a cellular product (MDG1015) consisting of New York esophageal squamous cell carcinoma-1 (NY-ESO-1)/L antigen family member 1a (LAGE-1a)-specific CD8+ T cell receptor-transduced (TCR-)T cells co-expressing the costimulatory switch protein (CSP) PD1-41BB, which turns an inhibitory signal mediated by the PD-1:PD-L1 axis into positive T cell costimulation. Methods: In vitro co-cultures of MDG1015 and PD-L1-positive or -negative target cells were used to analyze TCR-T cell functionality, such as TCR-T (poly-)cytokine release, the killing of target cells, and TCR-T proliferation. The safety of MDG1015 was evaluated via different panels of antigen-negative cell lines or primary cells expressing or lacking PD-L1. Results: Preclinical analyses demonstrated TCR-gated activation of the CSP, leading to enhanced functionality of MDG1015 against antigen-expressing, PD-L1-positive tumor cells without any impact on antigen-negative target cells. Conclusions: The favorable, preclinical functionality and safety profile qualifies MDG1015 as a promising cellular therapy for explorative clinical testing in hard-to-treat solid tumor indications. Full article

Background: It is estimated that most patients with severe sepsis are admitted through the emergency department. Early identification and subsequent early appropriate therapy remain cornerstones of sepsis management. Early recognition of sepsis in the emergency department (ED) is crucial. The National Early Warning Score 2 (NEWS2) has shown limitations in prognostic accuracy. We aimed to develop and evaluate a prognostic model combining NEWS2 with triage data to predict 28- and 90-day mortality in adult patients with bacterial sepsis. Methods: We conducted a retrospective cohort study of 557 patients admitted to the ED with suspected bacterial infection between March 2017 and September 2019. Candidate predictors included triage variables (vital signs, comorbidities, blood gas data) and clinical scores (NEWS2, SOFA, qSOFA, APACHE2, and SIRS). Outcomes were 28- and 90-day mortality. Logit analysis was used to develop prognostic models, with assessment of discrimination and calibration. Results: Overall mortality was 24.6% at 28 days and 36.4% at 90 days. Models combining NEWS2, age, and lactates outperformed NEWS2 alone (28-day: 73.8% vs. 69%; 90-day: 71.6% vs. 67%). Including terminal status further improved accuracy. Finally, this paper proposes new criteria for the early identification of patients with sepsis in triage, with positive outcomes. Conclusions: Combining NEWS2 with age and lactates enhances prognostic accuracy at triage. This model may inform improved sepsis management. Full article