Advancing Precision Oncology Through Artificial Intelligence
Expert Perspectives · Keira Smith · 2024-04-22
In this latest edition of The Way Ahead: The Convergence of Technology and Cancer Care, Dr. Waqas Haque shares his perspectives on machine learning models for classifying cancer immunophenotypes in lung cancer; Insilico Medicine’s artificial intelligence–driven process behind the development of INS018_055, a promising drug for idiopathic pulmonary fibrosis; the approval of lisocabtagene maraleucel for chronic lymphocytic leukemia/small lymphocytic lymphoma; and more!
Artificial intelligence (AI) corner: A recent study introduces two machine learning models aimed at classifying cancer immunophenotypes, potentially helping to identify non–small cell lung cancer (NSCLC) patients who could benefit from immunotherapy. The models, detailed in a recent publication by AI in Precision Oncology, utilize a digital pathology approach to assess the cellular composition of tumor immune microenvironments. The research focuses on identifying patients with an immune-excluded phenotype, crucial for predicting responses to immunotherapy. Transforming growth factor–beta (TGF-ß) signaling is known to promote immune-exclusion, where CD8-positive T cells are surrounding stroma but not within the actual tumor. By quantifying CD8 cell positivity, the models demonstrate promising accuracy comparable to pathologist annotations. This advancement underscores the role of AI in refining patient selection for tailored treatments, emphasizing personalized medicine’s potential in NSCLC care. The study marks a significant step towards precision oncology, emphasizing the importance of directing therapies to patients most likely to benefit, thus improving efficacy and minimizing side effects.
A recent paper in Nature Biotechnology by Insilico Medicine sheds light on the AI-driven process behind the development of INS018_055, a promising drug for idiopathic pulmonary fibrosis (IPF). Using their proprietary platform, Insilico identified the target TNIK and designed a novel small molecule through generative AI. INS018_055 has progressed through clinical trials with positive results, marking a milestone as the first AI-designed drug for an AI-discovered target to reach phase 2. This achievement demonstrates the potential of AI in accelerating drug discovery and offers a blueprint for future pharmaceutical applications. These results may signal good news to come regarding the nearly dozen oncology drugs in the company’s pipeline.
New approvals: Lisocabtagene maraleucel (Breyanzi®), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has received FDA approval for relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) after two prior lines of therapy, including BTK and BCL-2 inhibitors. In the TRANSCEND CLL 004 trial, 20% of patients achieved complete response with durable outcomes. Lisocabtagene maraleucel offers a one-time infusion, providing hope for patients with historically limited treatment options. Despite potential adverse events like cytokine release syndrome and neurologic toxicities, its approval signifies a shift towards personalized T-cell therapy for CLL/SLL, offering a promising option for patients facing relapsed or refractory disease.
In other news regarding CAR T, the New England Journal of Medicine reported a study of three patients with recurrent glioblastoma receiving treatment with CARv3-TEAM-E T cells, engineered to target epidermal growth factor receptor (EGFR) variant III and wild-type EGFR. Administered via intraventricular infusion, the therapy resulted in dramatic tumor regression without severe adverse events or dose-limiting toxic effects. The responses were transient in two out of three participants, but the open-label trial marks a step toward CAR T cell therapy for glioblastoma.
About Dr. Haque
Waqas Haque, MD, MPH, is a third-year Internal Medicine Resident at New York University (NYU) in a Clinical Investigator Track. He recently matched to the University of Chicago for fellowship, which he will be beginning later in 2024. As a Clinical Investigator Track Resident, Dr. Haque has balanced his patient care work with a variety of research projects. During his fellowship training at the University of Chicago, he plans to further his work in innovative clinical trial design, value-based care delivery to cancer patients, and clinical investigation.
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