CAR T cell therapy expands potential for solid tumor treatment

For several years, CAR T cell therapy has been one of the most effective immunotherapy approaches in oncology. The treatment involves genetically modifying T cells so they can recognize tumor-specific antigens and attack cancer cells directly. While the therapy has been mainly used for hematological cancers, researchers at Fraunhofer IZI and the University Hospital of Würzburg are now advancing it for the treatment of solid tumors such as ovarian, breast, and adrenocortical carcinoma.

Michael Hudecek is leading the research project in Würzburg and emphasizes: "We’ve already treated a number of patients with it, and initial results are promising. This is truly a glimmer of hope for patients with solid tumors."

A central element of this therapy is the use of ROR molecules found on the surface of cancer cells. These molecules are typically active during embryonic development but largely absent in adults, except in cases of cancer. By engineering CAR T cells to specifically recognize RORs, the therapy aims to selectively target tumor cells while sparing healthy tissue.

Another key development is the improvement of the manufacturing process. Instead of using viruses for genetic modification, researchers employ the Sleeping Beauty transposase enzyme. This allows therapeutic genes to be integrated into the genome more safely and cost-effectively. Hudecek notes: "This method has safety advantages and helps to reduce the amount of work and cost involved in production."

At Fraunhofer IZI, the team led by Kati Kebbel and Gerno Schmiedeknecht has established a robust cleanroom process that meets strict pharmaceutical standards. Schmiedeknecht explains: "In terms of pharmaceutical quality and safety, the process meets the strict standards that apply to the approval of drugs for use in clinical trials. This enables translation into the clinic and first treatment of patients."

The CAR T cells are derived from patients’ blood through a multi-step process:

• Leukocyte collection: White blood cells are enriched at the clinic to produce a leukocyte concentrate.
• Isolation: T cells are separated using paramagnetic particles and magnetic columns, achieving up to 98 percent purity.
• Genetic modification: The Sleeping Beauty enzyme is used to insert CAR receptors into T cells.
• Expansion: The modified cells are cultured for about ten days, harvested, and stored frozen in liquid nitrogen.
• Administration: Patients receive the therapy via infusion at the hospital.

While more clinical development is required, early results are encouraging. Hudecek stresses the significance of these advances: "Our research in this field demonstrates that here in Germany, we are able to develop even highly ambitious medical therapies and put them into clinical practice quickly and to the very highest standards of quality."

The therapy holds promise not only for patients with different forms of cancer but also for those with autoimmune disorders and infectious diseases.

MEDICA-tradefair.com; Source: Fraunhofer