Cancer immunotherapy articles from across Nature Portfolio

Two seminal studies report a bioengineering approach to modeling CAR-T cell therapy of solid human tumors.

Neoadjuvant chemoradiotherapy has become the standard of care in patients with resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC). Here, authors present a randomised phase II trial reporting the non-inferiority of neoadjuvant camrelizumab (anti-PD-1) and chemotherapy (nab-paclitaxel and cisplatin) compared to chemoradiation (nab-paclitaxel, cisplatin, and radiotherapy in patients with resectable LA-ESCC.

Wang and colleagues report the clinical results and immunological correlates of a phase 2 clinical trial of cryoablation plus lenvatinib and sintilimab in persons with advanced or metastatic intrahepatic cholangiocarcinoma.

Promising clinical activity of Claudin (CLDN) 18.2-directed CAR-T cell therapy in patients with gastric cancer has been recently reported, however gastrointestinal toxicities have also been described. Here the authors recapitulate the on-target off-tumor toxicity of CLDN18.2-directed CAR-T cells due to gastric mucosa damage in preclinical models, suggesting an AND-gate strategy targeting CLDN18.2 and mesothelin to overcome CAR-T cell toxicity

Claudin 18.2 (CLDN18.2) has emerged as a target for gastrointestinal cancer, however, on-target/off-tumor toxicities have been also reported. Here, after reporting evidence of erosive gastritis in patients treated with CLDN18.2 targeted immunotherapies, the authors develop and characterize CLDN18.2 fully-human VH-only single domain CARs, showing that a lower affinity CAR mitigates on-target/off-tumor toxicity while preserving anti-tumor efficacy in gastric cancer models.