Towards ‘off the shelf’ allogeneic CAR T cells
Michael Hudecek (Germany): “The current state of the art is that almost all clinical trials use autologous CAR T cells, so derived from the patient. Also, in some settings, patients that have undergone prior bone marrow transplantation, the hematopoiesis is of donor origin. Still, it is a personalized cell product for one individual patient.”
There are efforts to generate ‘off the shelf’ allogeneic CAR T products derived from healthy donors. These could be applied in patients that have been so heavily pretreated with chemotherapy that producing autologous CAR T cells is not a viable option or simply because ‘off the shelf’ allogeneic products may be much cheaper and faster. The challenges to overcome here are the immunogenicity (i.e., the cells will eventually be rejected) and batch-to-batch variation.
Claire Roddie (UK) presented two ‘off the shelf’ allogeneic approaches that are explored at UCL. A key component of both approaches is downregulating T cell receptors using genome editing (UCART19 study) or Golgi retention (KCAR19 study), thus tackling the risks of rejection and graft-versus-host reactions that are associated with allogeneic approaches. This work was presented in more detail by Roddie’s collaborator Waseem Qasim (see 'Genome-edited allogeneic CAR T cells').
The group of Sarah Tettamanti (Italy) is collaborating with scientists from Bergamo to develop cord blood-derived CIK cells from HLA-matched donors as an off the shelf therapy for AML. This approach appears to be feasible and the cells show anti-AML activity.
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