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Sirolimus-generated donor Th2 cells are an investigational adoptive cellular immunotherapy consisting of allogeneic donor T cells that have been cultured *ex vivo* in the presence of interleukin-4 (IL-4) and sirolimus (rapamycin). Sirolimus, a potent inhibitor of the mechanistic target of rapamycin (mTOR), is used during the manufacturing process to selectively inhibit the differentiation of proinflammatory Type 1 (Th1) and Type 1 cytotoxic (Tc1) T cells. This process biases the T-cell population toward a Type 2 (Th2) helper phenotype, which is associated with the production of anti-inflammatory cytokines. When infused into patients following allogeneic hematopoietic stem cell transplantation (HSCT), these cells are intended to modulate the recipient's immune system, reducing the incidence and severity of graft-versus-host disease (GVHD) by shifting the immune environment from a Th1/Tc1-mediated inflammatory state to a Th2-mediated regulatory state. Importantly, this approach seeks to preserve the graft-versus-tumor (GVT) effect, as the GVT response can be mediated by non-mTOR dependent pathways or specific Th2 subsets.
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