21.01.2025
Immunologcially multicompatible cellular products
Life Sciences, Onkologie
- Single editing process and better safety profile
- Escape from NK-mediated recognition
- Preservation of cellular physiology
Ihr Kontakt
Dr. M. Charlotte Hemmer
- E-Mail:
- chemmer@baypat.de
- Telefon:
- +49 (0) 89 5480177 - 29
- Referenznummer:
- B83148
Factsheet
Download Tech Offer (PDF)Herausforderung
Adoptive transfer of T-cells has proven to have tremendous potential for treating cancer, infections and autoimmune disease. However, in order to prevent rejection of transferred T-cells, the polymorpic human leukocyte antigens (HLA) between donor and recipient T-cells need to be matched. This calls for a high degree of personalization. Therefore, the last years have proposed many approaches to generate universal or at least broadly applicable allogeneic donor cells. Generating autologous T cell products is time-, labor- and cost-intensive. One approach to generate universal donor cells is knocking out HLA class I and II through targeting of beta-2-microglobulin and transcription factor CIITA. Although HLA KO abrogates allogeneic T-cell responses, it elicits NK-cell recognition. To avoid this, many genomic alteration are needed, e.g. fusion construct of HLA-E and beta-2-microglobulin, prolonging and complicating the clinical application of these T cells.
Innovation
It was succesfully shown that a reduction of the diversity of HLA molecules by selective editing of HLA class I molecules can be achieved in primary human T cells in a single editing event and results in inhibition of T-cell alloreactivity and NK-cell recognition simultaneously, but also preserves the T-cell graft’s canonical HLA class I expression. In the presence of allogeneic T cells and NK cells, T cells with remaining expression of a single, matched HLA class I allele show improved functionality in vivo in comparison with conventional allogeneic T cells.
Kommerzielle Möglichkeiten
- Single step editing process with reexpression of defined antigen receptors
- Escape from NK-cell mediated recognition and inhibition of T-cell alloreactivity
- Better safety profile by maintaining T-cell graft's canonical HLA class I expression
- Preservation of cellular physiology as unique advantage
Entwicklungsstatus
TRL Level 3