Tumor Infiltrating Lymphocytes (TIL), isolated and expanded from fresh tumor material can be a potent immunotherapeutic treatment option for metastatic melanoma patients. This treatment, developed at the National Cancer Institute, Bethesda, MD, is now used in several centers in the US, Europe and Israel. Our team has implemented the so-called "young TIL" process in the BTU facility.
The BTU is producing TIL products for an European multi-center phase III trial with TIL therapy which started in 2014.
Infusion of patient T cells that have been genetically modified with tumor-reactive T cell receptors (TCR), so called TCR gene therapy, is an appealing immunotherapeutic strategy. TCR gene therapy can be used when tumor material is not available for the isolation of tumor-reactive T cells or in case tumor-reactive T cells cannot be expanded from such material.
In addition, TCR gene therapy allows the use of a set of particularly effective TCR genes in large patient groups. Furthermore, TCR gene therapy has the potential to treat patients with T cell populations that have an increased capacity for long-term engraftment, relative to the highly differentiated cell populations that are generally found within TIL.
The BTU has designed and validated a process to retrovirally transduce autologous T cells with a tumor specific TCR. This process is now used to produce cell products for a phase I/II trial in metastatic melanoma patients, conducted at the NKI-AVL in Amsterdam.
Circular plasmid DNA, produced and isolated from Escherichia Coli, has several appealing clinical applications. The BTU is able to produce GMP grade plasmid DNA that can be used in clinical trials.
Several DNA products that have been produced by the BTU have been used for a DNA vaccination trials at the NKI-AVL.
Besides DNA vaccination, plasmid DNA can also be used to genetically modify target cells as an alternative for expensive and laborious viral vectors.
In collaboration with NKI-AVL scientist, medical doctors and other collaborators, we are constantly exploring new treatment options. Together with the NKI-AVL and NEON Therapeutics (Cambridge, MA) we are currently developing a neo-antigen directed T cell product. This will hopefully result in a new generation of personalized T cell therapy.