Genetically engineered stem cells to boost cancer immunotherapy

The CSIC, the Banc de Sang i Teixits de Catalunya and the Idibell have signed an agreement to research the production of CAR-NK cells, which are easier to produce than the CAR-T cells used successfully in immunotherapy. The research will test stem cell editing using two technologies patented by the CSIC. One of the goals is to create a bank of CAR-NK anti-tumour cells for immediate use.

Recreación digital de células madre. / Adobestock

The CSIC, the Banc de Sang i Teixits (BST) from Catalonia and the Institut d'Investigació Biomèdica de Bellvitge (Idibell) have signed an agreement to investigate the genetic modification of stem cells obtained from umbilical cord blood to produce CAR-NK immune cells capable of recognising and attacking tumour cells and other diseases.

The research aims to improve the results of CAR-T (chimeric antigen receptor T-cell) therapies, which are already in use for some types of cancer. The main difference is that NK (Natural Killer) cells are easier to produce on a large scale from stem cells than T cells.

The agreement aims to create a bank of CAR-NK cells containing a battery of anti-tumour genes, including CAR19 or CAR19/20 receptors. The latter are genetic modifications that allow immune cells to specifically identify and attack acute lymphoblastic leukaemia and B-cell lymphoma. The aim is to store these cells in cell banks and make them available for immediate application in cancer immunotherapy treatments.

Two patented technologies developed at the CSIC

To this end, the CSIC will make available to the project the two patented technologies developed at the Margarita Salas Biological Research Centre (CIB-CSIC) by the team led by researcher Daniel Bachiller, which make it possible to introduce genetic modification into immune cells to make them capable of recognising and attacking tumour cells.

"We think that our development will make it possible to produce immune system cells designed to attack specific therapeutic targets in a much faster, more effective and cheaper way than the technologies currently being tested. Our system can also be applied to other diseases, such as fungal infections or those caused by antibiotic-resistant bacteria," explains Daniel Bachiller, explains Daniel Bachiller, who heads the Advanced Therapies group at the CIB Margarita Salas centre.

"Our method an also be applied to other diseases, such as fungal infections or those caused by antibiotic-resistant bacteria”, explains CSIC scientist Daniel Bachiller.

For its part, the BST, through the Cell Therapy Service (iPS and Advanced Therapies group, in collaboration with the group Manufacturer of Advanced Therapies), will provide induced pluripotent stem cells from umbilical cord blood and produce NK cells from them. IDIBELL, through the laboratory of immunotherapies against cancer, which is also attached to the Catalan Institute of Oncology (ICO), will provide models for in vitro and in vivo validation of new therapies.

A preliminary research project

CAR-NK (chimeric antigen receptor NK cells) therapies are a promising cancer-fighting strategy still in development. They are based on modifying NK cells (natural killer cells, a type of lymphocyte) so that they are able to recognise and specifically attack cancer cells.

The research of CSIC, BST and IDIBELL, which is preliminary and exploratory, aims to obtain and modify these cells from umbilical cord stem cells, and afterwards to test their viability and effectiveness in the laboratory.

Stem cells used in this project, and therefore the NK cells derived from them, are from donors compatible with a high percentage of the European population. As a result, the cells can be produced and stored for the patients who need them.

Nowadays, patient's own lymphocytes are used to produce CAR-T cells. Therefore, the cells have to be extracted, modified and cultured individually, "which makes the procedure extremely expensive and delays its application dangerously," says Bachiller.

This research aims to confirm whether it is possible to improve the efficacy of current cellular immunotherapy treatments by introducing a battery of anti-tumour genes into immunocompatible NK cells in order to boost the effect of CAR.

The resulting cell bank, which will be housed at the BST, is expected to contain modified cell lines of the most common genetic types. This would provide an immediately available CAR-NK cell bank for the treatment of acute lymphoblastic leukaemia and B-cell lymphoma.

 

Comunicación CSIC / Delegación en Cataluña

 

 

 

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