T cell receptor gene therapy for leukemia patients

In collaboration with Medigene AG and Miltenyi Biotec, we have initiated a phase I/II clinical study involving T cell receptor (TCR) gene therapy to treat patients with leukemia. This therapy uses engineered T cells that express a tumor-specific TCR. The LUMC previously conducted the first phase I/II gene therapy study for leukemia patients in the Netherlands. Building on the experience and results from that initial study, we are now launching a new phase I/II clinical trial.

Medigene (MDG) has extensive experience in TCR gene therapy, as they are currently running a phase I/II study treating patients with acute myeloid leukemia using TCR-modified T cells. Their expertise in process development for gene-modified products has been a valuable contribution to the quality of this project. In the preclinical phase, we validated and optimized the production process of the TCR T cell product in accordance with good manufacturing practice (GMP) regulations. Together with MDG, we completed the necessary documentation and validation runs, which led to approval from national authorities to begin the clinical phase I/II study.

After recruiting the first patient, who suffered from relapsed leukemia following an allogeneic stem cell transplant, MDG unfortunately decided to withdraw from the project. Fortunately, Miltenyi Biotec stepped in, allowing the study to continue. However, six months later, Miltenyi decided to initiate a phase I/II study using the same TCR but with a lentiviral vector. Miltenyi and LUMC invested considerable effort into optimizing viral titers, significantly improving the expression of TCRs encoded by lentiviral vectors.

As a result, we are now preparing to launch a phase I/II TCR gene therapy study for B-cell malignancies in collaboration with Miltenyi. The GMP virus is ready, and we are currently performing the final validation runs. We expect to start the clinical study in Q1 2025.