Cancer therapy articles from across Nature Portfolio

l-Asparaginase (L-ASP) is a standard therapy for leukemias but not solid tumours. In a compassionate-use trial for nasopharyngeal carcinoma, Chang et al. report that L-ASP enhances the anti-tumour T cell response with clinical benefits when combined with pembrolizumab. This study provides proof of concept for ‘metabolic-immunotherapy’ in cancer.

Traditional antibody–toxin conjugates (ATCs) are designed to target and destroy cancer cells. We present an ATC that acts on innate immune cells to promote tumor-cell phagocytosis and facilitate the translocation of tumor-derived antigens from phagolysosomes into the cytosol, where antigen cross-presentation and immune activation occur.

In a recently reported study, a novel engineered oncolytic Newcastle disease virus encoding porcine α1,3-galactosyltransferase was evaluated in monkeys with CRISPR-induced primary hepatocellular carcinoma and in a phase I clinical trial. The virus induced hyperacute tumour rejection and an objective response rate of 35% in 20 evaluable patients. This approach highlights the promises and challenges of oncolytic virus drug development.

LKB1-mut has been shown as a major genetic driver of primary resistance to immune checkpoint inhibitors. Here this group reports the identification of the LKB1-IAP-JAK dynamic complex as a molecular determinant for immune response of LKB1-mut lung cancer cells.

Yang et al. developed a proteolysis-targeting chimera (PROTAC) 753b, which targets BCL-xL and BCL-2 to the E3 ubiquitin ligase VHL, and showed that it removed senescent cells specifically from the liver, reducing the progression of chronic metabolic liver disease to liver cancer.

l-Asparaginase (L-ASP) is a standard therapy for leukemias but not solid tumours. In a compassionate-use trial for nasopharyngeal carcinoma, Chang et al. report that L-ASP enhances the anti-tumour T cell response with clinical benefits when combined with pembrolizumab. This study provides proof of concept for ‘metabolic-immunotherapy’ in cancer.

Traditional antibody–toxin conjugates (ATCs) are designed to target and destroy cancer cells. We present an ATC that acts on innate immune cells to promote tumor-cell phagocytosis and facilitate the translocation of tumor-derived antigens from phagolysosomes into the cytosol, where antigen cross-presentation and immune activation occur.