New Research Advances Cancer Immunotherapy Through Clinical Data, Resistance Mechanisms, and Microbiome Insights
New clinical data for ANKTIVA immunotherapy in lung cancer, a study on EBV-driven resistance via ADAR1 RNA editing, and research on microbiome metabolites modulating immunotherapy response were presented at major conferences and in recent publications.
Recent scientific presentations and published studies are expanding the understanding of cancer immunotherapy through new clinical trial data, discoveries about viral-induced treatment resistance, and investigations into the role of the microbiome.
ImmunityBio presented new Phase 3 clinical data for its IL-15 receptor agonist immunotherapy, ANKTIVA (nogapendekin alfa inbakicept-pmln), at the ASCO 2026 annual meeting. The data included results from two randomized trials in non-small cell lung cancer (NSCLC). The ResQ201A trial evaluated ANKTIVA combined with tislelizumab and docetaxel versus docetaxel alone for advanced or metastatic NSCLC that is resistant to immune checkpoint inhibitor (ICI) therapy. The QUILT-2.023 trial assessed ANKTIVA with a checkpoint inhibitor, with or without chemotherapy, for first-line NSCLC. ANKTIVA is designed to activate natural killer (NK) cells, CD4+ and CD8+ T cells, and memory T cells to restore immune function. The company also presented a matched adjusted indirect comparison of ANKTIVA plus BCG versus pembrolizumab for BCG-unresponsive non-muscle invasive bladder cancer.
Separately, a study published in Nature details a mechanism by which Epstein-Barr virus (EBV) drives tumor resistance to immunotherapy. The research demonstrates that the viral protein EBNA1 enhances the activity of the RNA-editing enzyme ADAR1. This elevated ADAR1 increases A-to-I RNA editing within double-stranded RNA near interferon-associated genes, which masks immunostimulatory signals and blunts interferon pathways, leading to reduced CD8+ T-cell infiltration and accelerated tumor growth. Combining an EBNA1-targeting degrader molecule, EP-1215, with an anti-PD-1 antibody effectively restored interferon signaling and suppressed EBNA1-positive tumors in humanized mouse models.
Another body of research highlights how metabolites produced by gut bacteria can modulate the response to cancer immunotherapy. A review article synthesizes findings from multiple studies showing that metabolites like short-chain fatty acids (SCFAs) and indoles can have either immunostimulatory or immunosuppressive effects. For example, butyrate, an SCFA produced by microbial fermentation, has been associated with improved responses to anti-PD-1 therapy in models of melanoma, non-small cell lung cancer, and colorectal cancer. Other studies have shown that specific microbial metabolites can influence the efficacy of adoptive T cell therapy and anti-CTLA-4 therapy.