On June 5, 2023 Vycellix, Inc., a transformational cell and gene engineering company with the mission to integrate its process-enhancing tools into the development and commercialization of next-generation, donor-derived medicines, including off-the-shelf T cell and natural killer (NK) cell-based cancer therapeutics, reported that its founding Chairman & CEO, Evren Alici, M.D., Ph.D., presented pre-clinical, proof-of-concept results for the Company’s single-step approach to engineer allogeneic cells (VY-UC) at the International Society for Cell & Gene Therapy (ISCT) Annual Meeting in Paris (Press release, Vycellix, JUN 5, 2023, View Source;utm_medium=rss&utm_campaign=vycellix-presents-proof-of-concept-data-for-vy-uc-allogeneic-cell-therapy-platform-at-the-international-society-for-cell-gene-therapy-isct-annual-meeting-paris [SID1234632482]).
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In an oral presentation during "Chief Scientific Officer Showcase", titled "Generation of Universal Cellular Grafts Utilizing Signaling Deficient Membrane-Bound CD45-Engagers", Dr. Alici debuted data showing that the insertion of a novel CD45-engager (VY-UC) into virtually any cell holds the potential to displace complex and costly gene-editing systems such as CRISPR-Cas9 to engineer fully immune privileged cells that in pre-clinical in vitro and in vivo models demonstrate persistence, retention of function, and avoidance of host immune rejection.
Dr. Alici’s studies, conducted by the Cell & Gene Therapy Group, which he leads at Karolinska Institutet (KI), Stockholm, Sweden, potentially position VY-UC as a preferred efficient and cost-effective off-the-shelf cell engineering strategy by focusing on the spatial abrogation of a functional immune synapse against the graft to avoid patient rejection responses towards cellular effector grafts (the donor-derived cells), while retaining the effector graft’s function. CD45-engagers were expressed on multiple cell types, including primary T cells, CAR-T cells, primary NK cells, CAR-NK cells, hepatocytes, and hematopoietic stem cells, and in each series of cell type evaluations, functional immune synapse formation was prevented, resulting in abrogation of cellular immune response, thus, eliminating the risk of graft rejection.
The VY-UC Abstract was recently published in a supplemental version of Cytotherapy (Volume 25, Issue 6 Supplement, S13-S14, May 2023) the official journal of ISCT: View Source(23)00148-2/fulltext
Dr. Alici fielded the following question at ISCT in summarizing the potential broad-reaching impact for VY-UC to redefine the paradigm for engineering "off-the-shelf" donor-derived medicines:
Q: There are multiple gene-editing strategies that claim to solve the challenges associated with engineering donor-sourced therapies, so why is VY-UC potentially disruptive?
A: "The goal for engineering any allogeneic cell is to overcome the risk that the patient’s immune system will recognize and eliminate the donor-sourced foreign cells. Unfortunately, allogeneic cell therapy studies to date do not appear to yet match up to the outcomes achieved by autologous products, especially when measuring cell persistence and durable outcomes. With our single-step CD45-engager program, we can completely avoid using any gene-editing system to ‘knock-out’ HLA Class I and II molecules, nor do we need to ‘knock-in’ any inhibitory ligands. We do not target to kill the host alloreactive population, either. We believe that Vycellix’s VY-UC platform has the potential to transform virtually any donor cell with a simple single transgene to become ‘stealth’ by preventing functional immune synapse formation in a single direction, and thus, avoid donor cell rejection. Our studies have shown complete escape from host-mediated rejection in many types of VY-UC engineered cells, including T cells and NK cells with these effector cells retaining their fitness and cytotoxicity, thus conserving viability, functionality and persistence. We are now preparing to advance the VY-UC platform into human clinical trials for off-the-shelf NK cell therapies targeting cancers, as well as preparing to partner and license our platform for T cell applications," explained Dr. Alici.
Vycellix’s platforms were all discovered by scientists at the world-renowned Karolinska Institutet (KI) in Stockholm, Sweden. The Company is also a collaborative partner in "NextGenNK", an international Competence Center for the development of next-generation NK cell-based cancer immunotherapies based at KI and funded by Sweden’s innovations agency, Vinnova. KI is globally recognized for its Nobel Assembly, which awards the Nobel Prize in Physiology or Medicine.