Immune oncology drug programs are increasingly moving towards use of allogeneic T cells which can be engineered and used with unmatched recipients. Celyad, for instance, recently got clearance for trial of one such product. Cellectis is working on similar approaches. These are moving toward being "off-the-shelf" cell products. But I wonder how scalable these approaches really are. Is it possible, for instance, to isolate/expand enough T cells from just one donor to accomplish adoptive transfer to 10 patients? to 100 patients? to 1000 patients? Or will more frequent donations and small batch processing be needed to make these technologies viable? Thanks in advance to anyone who has insight on this question.
Agree with @Alex Kashkin. Primary T-cells are not proliferating indefinitely (unless of course they are transformed like leukemic cells, e.g. Jurkat). We showed in a previous paper that in one patient, T-cells transduced with an IL15 retrovirus grew for a year and retained some T-cell functionality (LC15 cells) however I do not think it would be safe to use them as an adoptive transfer platform. One possibility could be to use HSC or iPSCs as a universal donor source but more safety issues, proper production protocols and long term characterization need to be developed.
HLA match is an important issue for allogeneic transplantation of any type of nucleated cell. There is need for a wide collection for "off-the-shelf" use or a method to prevent the expression of MHC on the surface of cells. Also, ways/methods to block mutations have to be standardised as the cells have potential of having mutations in long term culture conditions. Opinion of an immunologist..
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