Stanford University has launched a Phase 1 clinical trial to evaluate the safety and therapeutic potential of chimeric antigen receptor T-cell (CAR-T) therapy targeting the B7-H3 antigen in pediatric patients with solid tumors. The first patient received treatment in September 2024, marking a significant step in addressing the challenges of treating solid tumors with CAR-T cell therapy. This trial offers hope for patients with relapsed or refractory cancers who have not responded to conventional treatments.
Targeting B7-H3 in Solid Tumors
The CAR-T cells used in this study are engineered to target the B7-H3 antigen, a protein expressed on the surface of many solid tumors and some brain tumors in both children and adults. By targeting B7-H3, the CAR-T cells can specifically recognize and destroy cancer cells while sparing healthy tissue. Sneha Ramakrishna, MD, principal investigator of the study and member of the Stanford Cancer Institute, emphasizes the potential of this approach, stating that it could provide a potentially curative treatment option for a variety of pediatric and adult tumors, especially for those who have not responded to chemotherapy or have experienced relapse.
Enhancing CAR-T Cell Fitness with Dasatinib
One of the challenges in using CAR-T cell therapy for solid tumors is that chemotherapy can damage the patient's T cells, reducing the effectiveness of the CAR-T cells. To overcome this issue, Stanford researchers have incorporated dasatinib, a drug known to rest exhausted T cells, into the CAR-T cell manufacturing process. This results in healthier and more effective CAR-T cells that are better equipped to attack cancer cells. This enhancement is crucial for improving the efficacy of CAR-T cell therapy in solid tumor patients.
Trial Design and Patient Eligibility
The Phase 1 trial is currently enrolling patients aged 2-26 years with relapsed or refractory neuroblastoma, Wilm’s tumor, osteosarcoma, Ewing sarcoma, and soft tissue sarcomas. The trial will evaluate the safety of the therapy and observe therapeutic responses in these patients. Physicians who wish to refer patients can find the trial on clinicaltrials.gov (NCT06500819) and contact the study team to review eligibility criteria and arrange consultations.
Future Directions and Impact
In addition to assessing safety and efficacy, the trial will also investigate the factors that influence CAR-T cell function in patients. This knowledge will be used to refine and improve future CAR-T cell therapies for solid tumors. Ramakrishna highlights the importance of understanding the immune biology of CAR-T cells, stating that it is essential for developing the next generation of treatments. The ultimate goal is to make CAR-T cell therapy effective for all patients with solid tumors, expanding treatment options and improving outcomes.
