A 3-year-old boy with chemotherapy-resistant hepatoblastoma achieved a complete remission after two doses of experimental GPC3-CAR T cell therapy, according to a study published in the New England Journal of Medicine.
The case, reported by researchers at Baylor College of Medicine, Texas Children’s Hospital, and Seattle Children’s, involved a child who initially presented with a 11.2 cm (4.4-inch) liver tumor and lung metastases. The cancer had also spread to his bones, according to a report in the New England Journal of Medicine. Despite three rounds of chemotherapy and surgical resection, the cancer returned, prompting enrollment in the CARE study (NCT04715191), a Phase 1 trial testing GPC3-specific CAR T cells engineered with interleukin-15 and interleukin-21.
The treatment involved two outpatient infusions of CAR T cells derived from the patient’s own T cells, modified to target glypican-3 (GPC3), a protein overexpressed in hepatoblastoma. The therapy included a safety switch to regulate CAR T cell activity, a feature previously validated in preclinical models. After the first dose, imaging showed partial tumor shrinkage, and the second infusion led to complete remission, with no detectable disease 12 months later. The patient experienced no dose-limiting toxicities or cytokine release syndrome, a common complication in CAR T therapies for blood cancers.
CARE study reports complete regression of liver cancer in
This case demonstrates that a durable complete response in a chemotherapy-resistant solid tumor can be achieved entirely in the outpatient setting without systemic toxicity, said Dr. David Steffin, lead author and associate chief of cellular therapy at Texas Children’s. The patient’s tumor measured 11.2 cm by 9.6 cm by 7.1 cm (4.4 × 3.8 × 2.8 inches) at diagnosis, according to the study. Prior to enrollment, the child had undergone complete resection of the primary liver tumor and two lung metastases, but a new lung metastasis recurred, prompting participation in the CARE study.
The therapy was engineered from the patient’s own cells at the Good Manufacturing Practices laboratories at the Center for Cell and Gene Therapy using two vectors: one encoding the second-generation GPC3-CAR and the second encoding IL15, IL21, and the inducible caspase 9 safety switch, which Center for Cell and Gene Therapy investigators previously showed controlled CAR T expansion. Two infusions were administered eight weeks apart in the outpatient setting. A partial response was observed after the first infusion, and imaging showed complete resolution of the metastatic disease after the second infusion. Complete regression continues one year after treatment, as of the study’s publication in 2026.
Dr. Andras Heczey, a co-author and pediatric oncologist at Seattle Children’s, emphasized the potential of the therapy for GPC3+ solid tumors. This study provides evidence that these novel CAR T cells may be a safe and effective modality for hepatoblastoma and highlights the need for further assessment in patients with GPC3+ solid tumors, he stated. Heczey was at Baylor and Texas Children’s at the time of research. Other authors who contributed to this work include Amy N. Courtney, Michelle Choe, Nisha Ghatwai, Magdalena Abigail Esparza Cerda, Ramy Sweidan, Rajdekar Dhanashree, Huimin Zhang, Natasha Lapteva, Zhuyong Mei, Bambi J. Grilley, Leonid S. Metelitsa, Helen E. Heslop, and Malcolm K. Brenner, affiliated with one or more of the following institutions: Baylor College of Medicine, Texas Children’s Hospital, Center for Advanced Innate Cell Therapy at Texas Children’s Cancer Center, Center for Cell and Gene Therapy, Dan L Duncan Comprehensive Cancer Center, Seattle Children’s Hospital, and the University of Washington.
A 3-Year-Old's Metastatic Cancer Disappeared After Two Doses of
Researchers noted the engineered T cells’ longevity, bolstered by interleukin-15 and interleukin-21, as a key factor in sustained remission. However, the study’s single-patient scope underscores the need for larger trials, such as the ongoing IMPACT study at Seattle Children’s, to validate these results. The CARE study (NCT04715191) is a first-in-human, Phase 1 trial evaluating GPC3-CAR T cells armed with IL15 and IL21.
While the case offers hope, experts caution against overinterpretation. Liver cancer, the third leading cause of cancer-related deaths globally, has limited treatment options, particularly for advanced cases.
The findings, published in the New England Journal of Medicine, highlight the evolving landscape of immunotherapy for solid tumors and the importance of continued research in this field.