Paul-Ehrlich-Institut: Core activities within CARAT

The Paul-Ehrlich-Institut (PEI) is an internationally recognised medicines agency, responsible for the regulation of biomedicinal products and for conducting research in related areas. Research in the Section Molecular Biotechnology and Gene Therapy focusses on the delivery of therapeutic genes by viral vectors and in particular the surface engineering of viral vectors in order to achieve cell type specific gene delivery.

An important tool in the manufacturing process of CAR T cells are the vectors used for gene transfer and the conditions allowing high gene transfer rates. Usually, lentiviral (LV) or γ–retroviral vectors are applied. Both require that the T cells have been activated with cytokines to allow stable integration of the CAR gene into the genome. Maximized gene delivery rates can be achieved with transduction enhancers, such as retronectin or vectofusin, which enhance the colocalization between vector particles and cells. By surface engineering, this CARAT partner has generated LV vectors that use particular cell surface markers, such as CD4 or CD8, as entry receptors into T cells. Specificity for the targeted cell surface receptor is mediated by a high-affinity ligand, which can be a single-chain antibody displayed on the particle surface. These receptor-targeted vectors do not only deliver CAR genes selectively into specific subpopulations of T cells, but, in contrast to conventional LV vectors, also have the potential to reach non-activated resting T cells.

Within CARAT, lentiviral vectors targeted to subtypes of T cells will be evaluated for their potential to improve and facilitate the CAR T cell manufacturing process. Combination with transduction enhancers will be tested. Especially, vectors that deliver CAR genes directly into primary T lymphocytes that have not been activated before are highly promising in this respect. CAR T cells generated by this approach may be more potent and less exhausted.

Pei Pei entrance Cell culture Microscope
Paul-Ehrlich-Institut Profile

Question & Answers from the Paul-Ehrlich-Institut Team

Christian buchholz
Christian Buchholz
Head of Section
With the first CAR T cell products having achieved marketing authorization in the US, expectations are enormous that this novel concept in cancer therapy will become a breakthrough technology.
Jessica hartmann
Jessica Hartmann
Senior Postdoc
I am assessing all available information about clinical applications of CAR T cells in order to create status reports covering worldwide ongoing or completed trials.
Annika frank
Annika Frank
PhD student
Together with leading researchers and companies, we will bring this curative CAR therapy to patients suffering from cancer all over Europe.
Laura grimm
Laura Grimm
PhD Student
Working in a research project like CARAT gives the opportunity to not only share professional expertise but also get to know involved researchers on a personal level.
Tatjana weidner
Tatjana Weidner
Bachelor Scientist
I am proud to be part of such an innovative project with the ultimate goal of serving patients with so far incurable hematologic malignancies and solid tumors.