Clinical Trials

GPC3 IL15 and Dual IL15/IL21 CAR T cell therapy

The Heczey laboratory initially developed an IL15-armored GPC3-directed CAR T-cell therapy for children and young adults with relapsed or refractory GPC3-positive solid tumors.In these trials, the patient’s own T cells are reprogrammed to recognize and target a protein expressed by tumor cells called, glypican-3 or GPC3. Examples of tumor types that express GPC3 include hepatoblastoma, hepatocellular carcinoma, yolk sac tumor, rhabdomyosarcoma, and rhabdoid tumor.

The GPC3-CAR was further modified to express IL15 to enhance expansion, persistence, and metabolic fitness within the solid tumor microenvironment. This recently completed Phase 1 trial focused on evaluating safety, dose optimization, and preliminary signals of antitumor activity. The Heczey Lab has developed GPC3-CAR T cells that co-express IL15 and IL21. In addition to GPC3-CAR, T cells are armored with IL15 and IL21, proteins that help CAR T cells grow and work better. Patients who have been diagnosed with relapsed or refractory GPC3-positive solid tumors are potentially eligible for these trials. This therapy is currently under phase 1 clinical investigation at Seattle Children’s Hospital , Fred Hutch Cancer Center, and Baylor College of Medicine.

This next-generation construct was designed to further enhance CAR T-cell durability and functional persistence, with ongoing evaluation of safety, expansion kinetics, biomarker correlates, and early clinical responses in patients with relapsed or refractory GPC3-positive solid tumors. Currently all of our CAR T cell clinical trials for solid tumors are phase 1 clinical trials. Phase 1 trials focus on finding out how much of a therapy to give, how to give it, how often to give it and what side effects occur. For each trial, researchers are working to answer these questions:

  • Is T-cell therapy safe to give to children, teens and young adults with relapsed or refractory solid tumors?
  • What is the best dose of CAR T cells for patients with solid tumors?
  • Does T-cell therapy work against solid tumors?

Read more about these trial protocols at clinicaltrials.gov:

Learn more about this and other clinical trials at Seattle Children’s:

Relevant Publications

  • Interleukin-15-armoured GPC3 CAR T cells for patients with solid cancers

    Steffin D, Ghatwai N, Montalbano A, Rathi P, Courtney AN, Arnett AB, Fleurence J, Sweidan R, Wang T, Zhang H, Masand P, Maris JM, Martinez D, Pogoriler J, Varadarajan N, Thakkar SG, Lyon D, Lapteva N, Zhuyong M, Patel K, Lopez-Terrada D, Ramos CA, Lulla P, Armaghany T, Grilley BJ, Gottschalk S, Dotti G, Metelitsa LS, Heslop HE, Brenner MK, Sumazin P, Heczey A. Nature. 637(8047):940-946 (2025).

  • IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin

    Pang N, Shi J, Qin L, Chen A, Tang Y, Yang H, Huang Y, Wu Q, Li X, He B, Li T, Liang B, Zhang J, Cao B, Liu M, Feng Y, Ye X, Chen X, Wang L, Tian Y, Li H, Li J, Hu H, He J, Hu Y, Zhi C, Tang Z, Gong Y, Xu F, Xu L, Fan W, Zhao M, Chen D, Lian H, Yang L, Li P, Zhang Z. Journal of hematology & oncology. 14(1):118 (2021).

  • Glypican-3-Specific CAR T Cells Coexpressing IL15 and IL21 Have Superior Expansion and Antitumor Activity against Hepatocellular Carcinoma.

    Batra SA, Rathi P, Guo L, Courtney AN, Fleurence J, Balzeau J, Shaik RS, Nguyen TP, Wu MF, Bulsara CJ, Mamonkin M, Metelitsa LS, Heczey A. Cancer Immunology Research. 8(3):309-320 (2020).

  • Redirecting T Cells to Glypican-3 with 4-1BB Zeta Chimeric Antigen Receptors Results in Th1 Polarization and Potent Antitumor Activity

    Li W, Guo L, Rathi P, Marinova E, Gao X, Wu MF, Liu H, Dotti G, Gottschalk S, Metelitsa LS, Heczey A. Human Gene Therapy. 28(5):437–448 (2017).