On January 13, 2025, Stanford treated its first patient with Tecelra, an engineered T cell receptor (TCR) therapy that uses a patient’s own immune cells to target the cancer. Tecelra is a breakthrough treatment because it is the first FDA-approved engineered TCR therapy and the first drug to receive FDA approval specifically for synovial sarcoma, a rare type of soft tissue cancer that occurs in the muscle and ligaments. Tecelra is also the second cell therapy approved for solid tumors.
Stanford Cancer Institute member Nam Bui, MD, clinical associate professor and sarcoma specialist, says, “This is not just a breakthrough for sarcoma but for solid tumors in general.”
Tecelra works by engineering T cells to recognize MAGE-A4, a cancer cell antigen that is identified by the patient’s immune system. However, not all immune system subtypes can present the antigen, so patients need a specific HLA (human leukocyte antigen) subtype to be eligible for treatment. Additionally, patients must express the MAGE-A4 protein at a high level. Bui says that only about 20% of synovial sarcoma patients meet the eligibility criteria.
Stanford Cancer Institute member Allison Betof Warner, MD, PhD, director of Stanford’s solid tumor cell therapy program, says, “TCR cells are like CAR-T cells in that you engineer a naive T cell to express this receptor, but TCR cells can recognize intracellular antigens rather than just something on the surface of the cell, so it opens up a potentially new type of way to go after cancer cells.”
Researchers have been studying engineered T cells in various cancers for many years, and there’s excitement about learning more about how different immune subtypes and intracellular proteins interact. Betof Warner speaks to a TCR melanoma trial about to launch, which has shown early, promising results, and another ongoing TCR trial, launched by the same company that manufactured Tecelra, that targets a different protein present in various cancers. She is excited about future prospective TCR therapies that could recognize diverse malignancies and immune subtypes to help more patients, especially those with solid malignancies.
Stanford is one of 10 authorized Tecelra treatment centers in the country, with only two on the West Coast. Several patients are currently in the pipeline to receive the treatment at Stanford, along with many out-of-state referrals.
Receiving the drug at Stanford is the result of collaboration between several teams. Bui clears the patient from a sarcoma standpoint and Betof Warner confirms that they’re a good candidate to receive T cell therapy. If the patient is eligible for treatment, they’ll schedule the patient for apheresis, which is the process of retrieving the patient’s T cells. Engineering the extracted cells to target the MAGE-A4 antigen takes a few weeks. After the cells are ready, patients receive lymphodepletion chemotherapy to deplete their immune system so the patient’s immune system will not destroy the new cells when infused back into the patient. After infusion, the patient is required to stay at Stanford hospital for about a week while the new cells expand and their blood counts recover. The Stanford bone marrow transplant team uses their expertise in T cell infusions to help Betof Warner’s team monitor patients for side effects. Side effects can include cytokine release syndrome, an overactivation of the immune system, but this is generally short-lived, low grade, and can be managed with medicine.
Stanford participated in the clinical trial that led to FDA approval. 44 patients were treated during the trial, seven of them at Stanford. 43% of all patients saw their tumors shrink, and the median duration of response, which is how long after treatment the tumor stops growing, was six months (source).
Bui says, “This drug is basically validation that TCR therapy can work very effectively and the next step is to expand on that for additional targets. We also need to understand mechanisms of resistance in order to make patients’ responses more durable. We've had some patients who have had prolonged durable responses, but for others, the cancer can relapse quickly within a few months. How do we manage that? Do we try another target? There are all kinds of research questions.”
Betof Warner’s laboratory is examining patient samples to understand the mechanisms of resistance and who the treatment works well and who may not be the right candidate.
She says, “We’re really excited to iterate and learn from our patients who respond on why this works well. For the ones where it does not work well, we can learn how to improve upon this treatment. It speaks to Stanford’s leadership in the cell therapy space that we’re one of the earliest sites and leading the way on this treatment.”
