Immunotherapy for early-stage cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (CSCC) is a highly prevalent malignancy with rising incidence, particularly among elderly and immunosuppressed individuals. Although most early-stage cases are cured with surgery, a relevant minority present with high…

Phase 1/2 study of pegenzileukin, a pegylated recombinant non-alpha IL-2, with cemiplimab for the treatment of advanced unresectable or metastatic skin cancers

Background
Pegenzileukin (SAR444245), a pegylated non-alpha recombinant human interleukin (IL)-2 variant, avoids engagement of the IL-2 receptor α subunit (IL-2Rα) chain and associated toxicities, while retaining engagement of IL-2Rβ,…

Targeting VEGF signaling and stromal remodeling enhances chemoimmunotherapy efficacy in esophageal cancer

Background
Neoadjuvant chemoimmunotherapy (NACI) has shown promising results in treating esophageal squamous cell carcinoma (ESCC), yet the mechanisms driving its efficacy remain poorly defined, limiting further optimization of this regimen.

Methods
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Membrane-bound TRAIL-armoring augments CAR-T cells in mesothelin-positive solid malignancies

Background
Mesothelin (MSLN)-targeted chimeric antigen receptor (CAR)-T cell therapy shows an effective and long-lasting response in high MSLN-expressing tumors, but fails to treat tumors with heterogeneous levels of antigen expression. Here we descri…

Human CART22.19 therapy in refractory pediatric B-ALL: insights from a named-patient cohort

Background
CD19-directed chimeric antigen receptor (CAR) T-cell therapies have transformed the treatment landscape for pediatric B-cell acute lymphoblastic leukemia (B-ALL), yet relapses driven by antigen escape remain a major limitation. Dual-targeti…

Aberrant p53 fuels macrophage immunoregulatory polarization and refractory clinical outcome in urothelial carcinoma

Background
Urothelial carcinoma (UC) exhibits extensive infiltration of tumor-associated macrophages (TAMs). As the most frequently altered gene in UC, TP53 is recognized not only as a guardian of genomic integrity, but also as a potential architect o…

Immunological consequences of chemotherapy: implications for cancer immunotherapy

Despite the success of immunotherapy, chemotherapy remains the backbone of front-line therapy for most patients with cancer. Immune checkpoint inhibitors, T cell engagers, and adoptive cell therapies have traditionally been relegated to second-line or…

CD155 links tumor immunotype to epithelial-directed precision therapy beyond checkpoint inhibition in cervical cancer

Background
Despite its viral etiology and immunogenic features, cervical cancer shows limited and often short-lived benefit from programmed cell death protein 1 blockade, currently the only approved immunotherapy for this disease. This limitation high…

KLF4 overexpression in CAR T cells enhances antitumor potency by preventing exhaustion

Background
Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapy for patients with refractory or relapsed lymphoma or leukemia. However, inefficient activity and insufficient persistence of CAR T cells impede the durability of it…

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