GMP Development


Cell adapters pave the way for affordable cancer immunotherapy

3D Rendering of Natural Killer NK Cell Destroying Cancer Cell
© Alpha Tauri 3D -

The approvals granted for the first CAR (chimeric antigen receptor) T cell therapies have expanded the treatment options for various types of leukemia and lymphomas.

Alongside the optimization and automation of therapeutic procedures, the development of off-the-shelf products based on cells from the innate immune system, such as macrophages and natural killer (NK) cells, is increasingly shifting into the focus of research and development approaches. 

One such approach is the manufacture of CAR-modified NK cells from healthy donors (CAR-NK cells). These are emerging as a promising cell resource that can be manufactured and stored independently of the patient. This approach would significantly increase the availability of these therapeutic agents with regard to both time and quantity.

A further approach is being pursued by Heidelberg-based Affimed GmbH. The immuno-oncology company is developing bispecific antibodies, known as Innate Cell Engagers (ICE®), which act as adapters and establish a connection between cells from the innate immune system (e.g. NK cells) and tumor cells. The ICE® recognize CD16A on the NK cell on the one hand and a tumor antigen on the tumor cell on the other, bringing the NK and the tumor cell together. Within this complex, the NK cell is activated and kills the tumor cell. 

As part of a proof-of-concept study, the two approaches (CAR-NK and NK plus ICE®) will be evaluated at Fraunhofer IZI in cooperation with Affimed. NK cells from healthy donors will be isolated and modified to become CAR-NK cells designed to target a specific tumor antigen. Alongside this, NK cells will be incubated with a bispecific ICE®. The two cell preparations will subsequently be brought together with tumor-antigen-­positive tumor cells before being screened and compared in vitro for their phenotypic and cytotoxic properties. Moreover, the efficiency and the efficacy profiles of both approaches are to be evaluated in tumor xenograft models in the mouse.

The cooperation between Fraunhofer IZI and Affimed GmbH is expected to provide valuable insights into the mechanism of action and effectiveness of the approaches of both the CAR-NK cells and the ICE® combination, which can then be harnessed when developing the therapies against various cancer indications.