DRIVIN CAR

Acronym: DRIVIN CAR
Title: Developing robust in vivo nanomedicine-based chimeric antigen receptor technology

What is the DRIVIN CAR project about and what challenge does it aim to address?

The general aim is to develop a new type of nanomedicine to treat cancer patients. More specifically, we aim to generate a new method to deliver an existing immune-therapy to the patients. This type of immune-therapy, the so-called 'chimeric antigen receptor' (briefly 'CAR') technology already exists and has the potential to transform cancer management, but is currently held back by an inefficient and costly production process. We will develop a new method to deliver these CARs to the patients.

What are the key outcomes or innovations DRIVIN CAR hopes to achieve?

Immune-therapy is a type of therapy that helps the immune system to recognize and fight cancer cells. In the CAR-therapy, one genetically modifies immune cells on the cell surface with a CAR, so that these immune cells recognize unique proteins on the surface of the cancer cells. This immune cell/cancer cell recognition triggers the immune cells to get active and execute their cell-killing activities.

Currently, the immune cells are modified outside of the body, the so-called 'ex vivo' approach: the immune cells are extracted from the blood of the patient, modified in the lab to express the CAR, cultured for a long time to increase their numbers, and then re-infused in the patient. This is a strictly individual approach: for each individual cancer patient, a lab culture needs to be set up. The logistics of this approach is challenging, which makes this approach inefficient and very expensive.

In the 'DRIVIN-CAR' project we will modify the immune cells with the CAR 'in vivo', that is, in the bloodstream. To do this, we well design and optimize a nanomedicine. This nanomedicine, an ultra-small multicomponent complex, specifically delivers the genetic code of the CAR to the blood-circulating immune cells. In such a way we avoid the lengthy and ex vivo culture period. Patients will benefit from the CAR-therapy, but by receiving a simple injection of an 'off-the-shelf' medicine, instead of an infusion with cultured immune cells.

In this phase of the project we will design the nanomedicine and test it in animals. We hope that in a few years, this nanomedicine will be available for cancer patients and oncologists.

Which expertise will VUB bring to the table in this consortium?

VUB has two main tasks in the project. First, VUB will exploit its expertise in antibody-technology to optimize the nanomedicine. In the design it is indeed crucial that the nanomedicine is delivered to the correct type of immune cells. We will connect the nanomedicine to antibody-fragments, and test its delivery to different immune cells. Second, VUB will also help to test the efficacy of the therapy and generate tools to understand it better. We will track the CAR-modified immune cells in the animals by PET imaging, and will make dedicated radioactive probes for it.

 What broader societal impact will DRIVIN CAR have?

With DRIVIN CAR we aim to transform the field of CAR-based immune therapy and bring it to the patients at a reasonable cost. Currently, the cost of immune-therapy is so high that health organizations struggle to implement it further. With this we will give the ecosystem a push to expand the CAR-technology and make it more available, for more patients, for more cancer types, and make it more efficacious.