ArticleMolecular therapy. Oncology2024
Solid cancer-directed CAR T cell therapy that attacks both tumor and immunosuppressive cells via targeting PD-L1.
Article in Molecular therapy. Oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed.
- Perioperative myeloid cell remodeling shapes CAR-T cell efficacy in glioblastoma.Nature communications · 2026Article
- CAR-T cells directed toward PD-L1 demonstrate potent, antigen-specific activity against cholangiocarcinoma: A proof of concept study.Molecular therapy. Oncology · 2026Article
- The Conflicting Role of Myeloid Cells in CAR T-Cell Therapy.Cancer research · 2026Review
- Steroid receptor coactivators in immunity - From function to emerging translational opportunities.The Journal of biological chemistry · 2026Review
- Integrating CAR-T therapy with PD-1/PD-L1 blockade: Mechanisms, synergy, and optimized strategies in NSCLC.iScience · 2026Review
- Review
- Engineering Immunity: Current Progress and Future Directions of CAR-T Cell Therapy.International journal of molecular sciences · 2026Review
- Skeletal muscle dysfunction induced by cancer immunotherapy: mechanistics insights and surgical implications.Frontiers in immunology · 2026Review
- Targeting the Dynamics Between TAMs and CAR-T Cells in Solid Tumor Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- CAR-T cell therapy for pancreatic cancer: Translating emerging targets and dual-targeting strategies from solid tumors.Frontiers in immunology · 2026Review
- HMC3 revealed: how much do these "Microglia" really tell us?Frontiers in immunology · 2026Review
- Novel allogeneic CAR T-cell platform involving microhomology-mediated end joining repair and low off-targeting potential.Molecular therapy. Nucleic acids · 2025Article
- Exploring the TRIM15 protein interaction network as a drug target using machine learning in pancreatic cancer.Discover oncology · 2025Article
- Overcoming resistance to anti-PD-L1 immunotherapy: mechanisms, combination strategies, and future directions.Molecular cancer · 2025Review
- Chimeric PD‑1 receptor redirects primary T cells against childhood solid tumors but not to PD‑1 ligand‑positive CD80‑coexpressing cells.Molecular medicine reports · 2025Article
- Review
- Advancements in Gene Therapy for Non-Small Cell Lung Cancer: Current Approaches and Future Prospects.Genes · 2025Review
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Chimeric antigen receptor (CAR) T cell therapy has encountered limited success in solid tumors. The lack of dependable antigens and the immunosuppressive tumor microenvironment (TME) are major challenges. Within the TME, tumor cells along with immunosuppressive cells employ an immune-evasion mechanism that upregulates programmed death ligand 1 (PD-L1) to deactivate effector T cells; this makes PD-L1 a reliable, universal target for solid tumors. We developed a novel PD-L1 CAR (MC9999) using our humanized anti-PD-L1 monoclonal antibody, designed to simultaneously target tumor and immunosuppressive cells. The antigen-specific antitumor effects of MC9999 CAR T cells were observed consistently across four solid tumor models: breast cancer, lung cancer, melanoma, and glioblastoma multiforme (GBM). Notably, intravenous administration of MC9999 CAR T cells eradicated intracranially established LN229 GBM tumors, suggesting penetration of the blood-brain barrier. The proof-of-concept data demonstrate the cytolytic effect of MC9999 CAR T cells against immunosuppressive cells, including microglia HMC3 cells and M2 macrophages. Furthermore, MC9999 CAR T cells elicited cytotoxicity against primary tumor-associated macrophages within GBM tumors. The concept of targeting both tumor and immunosuppressive cells with MC9999 was further validated using CAR T cells derived from cancer patients. These findings establish MC9999 as a foundation for the development of effective CAR T cell therapies against solid tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.