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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

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

References

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