CAR-T cells, genetically engineered immune cells from patients in the laboratory, have proven effective in the treatment of certain forms of blood and lymph node cancer. But cancer immunotherapy can become even more effective. A joint clinical study of the Charité – Universitätsmedizin Berlin and the Max Delbrück Center has received millions in funding from the Federal Ministry of Education and Research.
CAR-T cell therapies are often the last resort for patients with certain forms of blood or lymph node cancer who do not respond to current treatments. Immune cells (T-cells) of the patients are equipped in the laboratory with a so-called chimeric antigen receptor (CAR) – a small sensor that scans body cells and searches for specific characteristics of cancer cells. Back in the patient’s body, they detect exactly the surface molecule they are targeted at and kill the tumour cells.
The research groups of private lecturer Dr. Uta Höpken and Dr. Armin Rehm at the Max Delbrück Center have developed an approach for a novel CAR-T cell therapy against a form of lymph node cancer that originates from B lymphocytes: B non-Hodgkin’s lymphoma. Under the direction of Prof. Dr. Ulrich Keller and Prof. Dr. Lars Bullinger at the Medical Clinic with a focus on haematology, oncology and tumour immunology at the Benjamin Franklin Campus of the Charité, the new immunotherapy is to be tested on humans for the first time in a phase I/IIa study. The joint project of the Charité and the Max Delbrück Center is funded by the Federal Ministry of Education and Research (BMBF) with 4.6 million euros. The ministry wants to launch therapies against diseases that are currently untreatable or difficult to treat.
Antigen CXCR5: Hard for a CAR to miss
The CARs approved so far for the treatment of blood and lymph node cancer mostly dock to the antigen CD19, a surface molecule of B cells that can change malignantly and become cancer cells. Dr Höpken and Dr Rehm have identified a molecule that is probably even more suitable as a target for a CAR to treat lymph node cancer: CXCR5. Unlike CD19, the amount of which on cancer cells can vary from patient:in to patient:in or even be lost, the molecule CXCR5 is found evenly on all mature lymph gland cancer cells. Moreover, it is not only found on tumour B cells, but also on certain T helper cells that support tumour growth. “These properties make CXCR5 a unique target for CAR-T cell therapies,” says private lecturer Dr Höpken. In mouse models, the researchers were able to show that the corresponding CAR-T cells find CXCR5 particularly reliably and destroy the tumour cells.
First applications in patients are imminent
Clinical studies must show whether the new immunotherapy is safe and also effective in humans. Charité Clinic Director Prof. Keller and his team are preparing the first studies with a few selected patients: “We are confident that we will be able to prove the safety of the new CXCR5-CAR-T cell therapy with this phase I study and also find the first indications of its effectiveness. Therapeutically addressing both the tumour cell and its supporting microenvironment is a promising and highly innovative approach.” As soon as the Berlin State Office for Health and Social Affairs (LAGeSo) has approved the production of the cell product and the Paul Ehrlich Institute (PEI) as the Federal Institute for Vaccines and Biomedical Drugs has approved the clinical trial, the recruitment of up to 24 patients will begin. The scientists expect this to be the case at the beginning of 2024. Initially, only patients who have not responded to standard therapy will be included.
New medicinal products are tested for safety and efficacy in a standardised procedure before they are approved for regular use. In a Phase I study, a therapeutic agent is used in humans for the first time – after extensive preliminary testing – in order to obtain preliminary data on tolerability and safety as well as further effects on the organism. The number of study participants is small. If no serious side effects occur and there are initial indications of possible efficacy, a phase II study follows. Here, the tolerability and side effects are determined in a somewhat larger number of patients and the dosage is optimised with regard to possible efficacy. Only in phase III trials, which often last for years and include a large number of participants, can the efficacy of the new substance be proven. For this purpose, the new substance is compared with other available and already approved drugs. Phase III trials provide the data needed for regulatory approval.
Photo Credit: CAR-T cells attack lymphoma cells © Max Delbrück Center | AG Höpken / Rehm
AG Rehm „Translationale Tumorimmunologie“
AG Höpken „Mikroumgebung als Regulator bei Autoimmunität und Krebs“
Mit scharfer Waffe gegen Lymphome
Die Trainerin: Porträt über Uta Höpken