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Transforming hematopoietic stem cell transplantation

Interview with Alain Vertès (Sloan Fellow, London Business School: Managing Director, NxR Biotechnologies GmbH, Basel, Switzerland), on the cell therapy industry and how it may offer potential for improved hematologic reconstitution and reducing graft-versus-host disease

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Jan 20, 2016
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Go to the profile of James L. Sherley, M.D., Ph.D.
James L. Sherley, M.D., Ph.D. almost 3 years ago

Very important area for discussion and innovation!

Let's think bigger and simpler for a moment. In most, if indeed not all, cases of allogeneic HSCT, the key therapeutic principle is the transferred HSCs. Now, sufficient matching is required for these crucial cells to be compatible for long-term engraftment and function in the recipient. Thereafter, as discussed here, GVHD, the attack of passively co-transferred donor immune cells directed against the recipient, must often be managed. As this discussion highlights, much effort is now placed on finding ways to moderate and ideally eliminate GVHD through biological strategies. But, what about a physical strategy? If there were a manufacturing process to remove the problem cells, would we be on our way to better allo-HSCT? Not so simple though, because the same cells responsible for GVHD have the complementary function of protecting the recipient patient from all sorts of infectious agents until new (but naive!) immune cells are produced by the co-transplanted HSCs and mature sufficiently to take over immune surveillance. An apparent "Catch 22."

Perhaps not so. If it were possible to isolate purer populations of allo-HSCs from preparations highly-enriched by selective expansion (an Asymmetrex technology), then we would only need to isolate the patient from infectious agents until their naive immune system matured. That maturation might be accelerated by exposing transplanted patients to non-infectious, but highly immunogenic antigens from pathogenic microorganisms.

This conceptually simpler regenerative medicine approach to reducing or eliminating GVHD may already be within reach by bringing together the indicated expertise:

1. Removal of allo-immune cells from HSC transplant preparations (likely to require HSC expansion and specific identification = Asymmetrex technologies)
2. Sterile isolation of transplant recipients
3. Acceleration of donor-derived immune system maturation in recipients

Thoughts?

James L. Sherley, M.D., Ph.D.
Director
Asymmetrex, LLC
http://asymmetrex.com/
jsherley@asymmetrex.com
617-990-6819