Advancing Precision Oncology Through Artificial Intelligence

Figure 1: Association between TGF-β gene expression signature and CD8 infiltration. Levels of CD8 were assessed by manual scoring of CD8 immunohistochemistry (IHC) and compared with a TGF-β transcriptomic signature from patient-matched tissue.

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! 

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.

For More Information

Pomponio RJ, Wang H, Bean SM, et al (2024). Classification of the tumor immune microenvironment using machine-learning-based CD8 immunophenotyping as a potential biomarker for immunotherapy and TGF-β blockade in nonsmall cell lung cancer. AI Precision Oncol. [Epub ahead of print] DOI:10.1089/aipo.2023.0008

Ren F, Aliper A, Chen J, et al (2024). A small molecule TNIK inhibitor targets fibrosis in preclinical and clinical models. Nature Biotechnol. [Epub ahead of print] DOI:10.1038/s41587-024-02143-0

Insilico (2024). Diversified pipeline discovered using pharma.ai. Available at: https://insilico.com/pipeline

Bristol Myers Squibb (2024). U.S. FDA approves Bristol Myers Squibb’s Breyanzi® as the first and only CAR T cell therapy for adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Available at: https://news.bms.com/news/corporate-financial/2024/U.S.-FDA-Approves-Bristol-Myers-Squibbs-Breyanzi–as-the-First-and-Only-CAR-T-Cell-Therapy-for-Adults-with-Relapsed-or-Refractory-Chronic-Lymphocytic-Leukemia-CLL-or-Small-Lymphocytic-Lymphoma-SLL/default.aspx

Choi BD, Gerstner ER, Frigault MJ, et al (2024). Intraventricular CARV3-TEAM-E T cells in recurrent glioblastoma. N Engl J Med, 390(14):1290-1298. DOI:10.1056/NEJMoa2314390

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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