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Lentiviral vector encoding interleukin-12 is an investigational ex vivo gene therapy developed by the University Health Network for the treatment of acute myeloid leukemia (AML). The therapy utilizes a third-generation, HIV-1-based lentiviral vector (pDY backbone) to transduce autologous AML cells with a fusion gene encoding human interleukin-12 (hIL-12) p70 and a mutant thymidylate kinase (TMPK) suicide gene. Upon reinfusion into the patient, the engineered leukemia cells secrete IL-12, which acts as a potent immunomodulator to stimulate NK and T cell proliferation, promote Th1 cytokine secretion, and induce a systemic anti-tumor immune response. The inclusion of the ΔLNGFR/TMPK cassette serves as a safety mechanism, enabling the selective elimination of the transduced cells through the administration of the prodrug zidovudine (AZT) in the event of adverse toxicities or insertional mutagenesis.
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