Astraveus enters CAR-T cell therapy manufacturing partnership with NecstGen

Paris-based Astraveus SAS  has partnered  with The Netherlands Center for the Clinical Advancement of Stem Cell and Gene Therapies (NecstGen) to evaluate a novel approach dubbed Lakhesys Benchtop Cell Factory^TM for the manufacturing of CAR-T therapies.

Though providing high response rates, CAR-T cell therapies have several problems such as autologous production at hospital sites driving cost of therapies or regulary induction of cytokine release syndrome (CRS).

Now, NecstGen will utilizse Astraveus’ Lakhesys Benchtop Cell Factory^TM at its facility in Leiden, to demonstrate its potential to significantly reduce costs and increase efficiency in CAR-T manufacturing in comparison to incumbent industry benchmarks. Additionally, NecstGen will produce lentiviral vectors for Astraveus’ internal research and development needs.

Astraveus recently demonstrated the potential of its platform with the first ever, end-to-end production of CAR-T cells within a microfluidic benchtop system and is now starting the external testing phase of its manufacturing platform. Astraveus’ is convinced that its platform simultaneously can decrease manufacturing costs as well as increase process efficiency and throughput many times over.

Novel vectors for CRISPR gene and CAR-T cell therapies

Further progress is reported by a group from the Helmholtz Center Munich. In Science Advances, the group led by Dong-Jiunn Jeffery Truong presented a new transport system for gene and cell therapy that overcomes the limitations of viral vectors such as AAV for gene therapy and lentiviral vectors for CAR-T cell therapy and enables the near-allogeneic production of CAR-Ts by eliminating immunogenic T cell proteins and the MHC I complex.

In vivo gene therapy for hereditary blindness corrected the defect in the Rpe65 gene 10 times more efficiently than was possible with viral vectors. An ex vivo therapy showed efficacy against cancer, but reduced unwanted immune reactions.

The new patented ENVLPE platform uses viral envelopes in which only correctly assembled gene-editing complexes are packaged, i.e. those from the Cas nuclease, the guide RNA strand and the editor RNA strand. The scientists achieved this by attaching an -RNA aptamer, which attached the ribonucleoprotein to proteins on the inside of the non-immunogenic virus-like particle. In addition, they stabilized the intrinsically unstable editor RNAs in the complex with a 3′ protective cap. The transport of a fully functional RNP to the site of action instead of the expression of proteins by AAV or lentiviral vectors reduces the probability of undesired immune reactions against the expressed proteins and those of the viral vectors to almost zero. This is because VLPs are not immunogenic. The scientists used the gene editors to switch off proteins on T cells that induce off-target immune reactions. By switching off the off-target immunity, the CAR-T cells can be produced centrally and cost-effectively.