A past Stanford study using engineered immune cells to treat pediatric solid tumors showed promising results in a mouse model. Now, that therapy is being tested in its first clinical trial. The phase 1 clinical trial will evaluate the safety of the therapy and observe a therapeutic response in pediatric patients. The trial’s first patient received their first treatment in September 2024.
The therapy uses chimeric antigen receptor T cells, or CAR-T cells, which are modified T cells from the patient’s body engineered to target specific markers on the cancer cells. CAR-T cells are grown in vitro and then infused into the patient to treat the cancer. This study’s CAR-T cells target the B7-H3 antigen on cancer cells. B7H3 is expressed in many solid tumors and some brain tumors in both children and adults.
Stanford Cancer Institute member Sneha Ramakrishna, MD, the study’s principal investigator, says that because B7-H3 is expressed on a variety of pediatric and adult tumors, cancer patients with diverse diagnoses could have access to a potentially curative treatment. This includes solid tumor patients who haven’t responded to chemotherapy and relapsed cancer patients whose cancer returned after a period of remission.
“Using the immune system to target these cancers is a novel way to think about treating them and will hopefully unlock a new treatment paradigm for our patients.”
While CAR-T cell therapy has shown efficacy in liquid tumors, solid tumors have proven a challenge for the treatment. Ramakrishna says that chemotherapy damages the T cells in solid tumor patients, so the CAR-T cells created from these damaged T cells are not very effective at attacking cancer cells. To mitigate this issue, Stanford researchers have made CAR-T cells more fit and healthy by incorporating dasatinib, a drug that rests exhausted T cells so they become healthier and produce stronger, more effective CAR-T cells.
Ramakrishna speaks positively about the advances made in cellular therapy in treating solid tumors, citing the recent FDA approvals of tumor-infiltrating lymphocyte (TIL) therapy for melanoma and MAGE-A4 TCR therapy for synovial sarcoma.
“There's a lot of movement in both understanding and having consistent clinical benefit for patients in the solid tumor field. I think we're right at the cusp of figuring out how to get these treatments to be effective for our patients, and we hope that this trial will contribute to that landscape and help expand treatment options for our patients.”
Patients are currently being enrolled in the phase 1 trial supported by the Stanford Center for Cancer Cell Therapy. Good candidates for the trial are relapsed and refractory patients aged 2-26 years diagnosed with neuroblastoma, Wilm’s tumor, osteosarcoma, Ewing sarcoma, and soft tissue sarcomas. The Stanford team will work with the patient’s primary team to decide if the patient may be eligible for the trial. Physicians who want to refer patients can find the trial on clinicaltrials.gov and email the contact to review the eligibility criteria and potentially set up a formal consultation with families.
In addition to evaluating safety and observing activity, the trial will also consider the signals and markers that make CAR-T cells work or not work in patients and how that knowledge can be used to improve future treatments.
“This is something that's very near and dear to my heart because the central focus of my research is understanding the immune biology of CAR-T cells in patients and use that to iterate and improve the next generation of treatments for the patients for whom we care. I'm also excited and privileged to be able to learn from every single one of our patients in a very deep and thoughtful way so that we can really understand what makes CAR-T cells work for our patients and then hopefully make them work for all of our patients.”
September 2024
By Katie Shumake
