Temporal optimization of CD25-biased IL-2 agonists and immune checkpoint blockade leads to synergistic anticancer activity despite robust regulatory T cell expansion

Background
Interleukin-2 (IL-2) immunotherapy can induce durable tumor remissions, but its clinical performance has been limited by significant drawbacks such as short serum half-life and high toxicity. Administration of IL-2 in complex with certain a…

Universal off-the-shelf combination immunotherapy using oncolytic viruses to redirect T cell engagers to target solid tumors

Background
Bispecific T cell engager (BiTE), such as blinatumomab, has demonstrated significant clinical success in treating hematological malignancies like B cell acute lymphoblastic leukemia and non-Hodgkin’s lymphoma. However, the application of Bi…

Histologic and immune characterization of cutaneous immune-related adverse events induced by immune checkpoint inhibitors

Background
Although immune checkpoint inhibitors (ICIs) are efficacious, they often cause immune-related adverse events (irAEs), most commonly cutaneous irAEs (CirAEs). The mechanisms underlying CirAEs remain unclear.

Methods
Attempting to better und…

Genetic drivers of tumor microenvironment and immunotherapy resistance in non-small cell lung cancer: the role of KEAP1, SMARCA4, and PTEN mutations

The tumor microenvironment (TME) plays a crucial role in shaping the response to immunotherapy in non-small cell lung cancer (NSCLC). While immune checkpoint inhibitors (ICIs) have revolutionized NSCLC treatment, a significant proportion of patients e…

Improved survival in advanced melanoma patients treated with fecal microbiota transplantation using healthy donor stool in combination with anti-PD1: final results of the MIMic phase 1 trial

Background
Microbiome manipulation research is focused on developing techniques to modify the gut microbiome and augment responses to immune checkpoint inhibitors (ICI). Fecal microbiota transplantation (FMT) represents a potential strategy to overcom…

An affinity-modulated T cell engager targeting Claudin 18.2 shows potent anti-tumor activity with limited cytokine release

Background
AZD5863 is a bispecific T cell engager (TCE) with high affinity to CLDN18.2 and low affinity to cluster of differentiation 3 (CD3), designed to decrease its peripheral cytokine release potential, improve the therapeutic index, and maintain …

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: results of the NEOMUN trial

Background
The phase II NEOMUN trial was conducted to investigate the therapeutic effect of preoperative programmed death receptor-1 inhibitor pembrolizumab for treating non-small cell lung cancer (NSCLC). Herein, we report the final efficacy, safety,…

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