Saturday, August 02, 2025

Scientists reprogram stem cells to generate continuous renewable cancer-fighting T cells

Good news! Cancer is history (soon)!

"... This approach suggests a new way to deliver immunotherapy, acting as an internal factory that produces tumor-targeting immune cells over time and potentially offering longer-lasting protection. ...

a novel strategy for treating hard-to-treat cancers, especially solid tumors that have proved to be more resistant to conventional T cell therapies. ..."

"In a first-of-its-kind clinical trial, ... scientists have shown it’s possible to reprogram a patient’s blood-forming stem cells to generate a continuous supply of functional T cells, the immune system’s most powerful cancer-killing agents. This approach suggests a new way to deliver immunotherapy, acting as an internal factory that produces tumor-targeting immune cells over time and potentially offering longer-lasting protection. ..."

From the abstract:
"Adoptive transfer of genetically engineered T cells expressing a tumor-antigen-specific transgenic T cell receptor (TCR) can result in clinical responses in a variety of malignancies. However, these responses are frequently short-lived, and patients typically relapse within several months. This phenomenon is largely due to poor persistence of the transgenic T cells, as well as a progressive loss of their functionality and terminal differentiation in vivo. This underscores the need for cell therapy approaches able to sustain the initial antitumor efficacy and lead to long-term antitumor efficacy.
Herein, we report the use of tandem cell therapies involving autologous T cells and hematopoietic stem cells engineered to express the NY-ESO-1 TCR for the treatment of solid tumors in a first-in-human phase I clinical trial ... This therapy is shown to be safe, feasible, and leads to initial tumor regression activity. T cell progeny from the HSC progenitors is shown to provide circulating transgenic NY-ESO-1 TCR-T cells, which display tumor-antigen-specific antitumor functionality, without any evidence of anergy or exhaustion. These results demonstrate the utility of transgenic HSCs to generate a self-renewing source of tumor-specific cellular immunotherapy in human participants"

UCLA scientists reprogram stem cells to create renewable cancer-fighting T cells | UCLA "First-in-human clinical trial demonstrates combining genetically engineered T cells and stem cells can produce cancer-fighting immune cells in humans"



Fig. 1: Overview of manufacturing protocol, and clinical trial procedures. Peripheral blood stem cells (PBSCs) were isolated from patients via leukapheresis following bone marrow mobilization with filgrastim and plerixafor. CD34+ cells are isolated via magnetic bead separation using the CliniMACS platform, and were then transduced with the lentiviral vector encoding the NY-ESO-1 TCR and sr39TK reporter/suicide gene (enabling non-invasive visualization of the transgenic HSC progeny in vivo within the bone marrow niche, as well as serve as a safety ablation feature), and were then cryopreserved. ...


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