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SPARK (Systemic Plasmid-Activated Response Kit) is an experimental intratumoral gene therapy designed to overcome the immunosuppressive tumor microenvironment and induce a systemic anti-tumor response. It consists of plasmids encoding the pro-inflammatory cytokine Interleukin-12 (IL-12), the T-cell-recruiting chemokine CXCL9, and a membrane-bound single-chain variable fragment (scFv) against CD3 (specifically clone 145-2C11 in preclinical models). Delivered via in vivo electroporation, SPARK aims to locally "inflame" the tumor lesion, recruit effector T cells, and provide a potent TCR-mimetic stimulus. This sequential activation leads to the expansion of tumor-specific T cells that can circulate and target distal, untreated lesions, a phenomenon known as the abscopal effect. Preclinical studies have demonstrated its efficacy in inducing regression of both treated and untreated tumors in various cancer models.
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