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TUMOR IMMUNOLOGY.pdf

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Tumor escape mechanism and T-cell adoptive<br />

immunotherapy after genetic manipulation<br />

(1) Tumor cells that produce TGFß that exert inhibitory effects on the immune system. Specific CTL can be genetically<br />

modified to become resistant to the TGFβ inhibitory effect through transgene expression of a mutant dominant-<br />

negative TGFß type II receptor (DNR).<br />

(2) Specific T cells genetically modified to produce IL-12 can overcome IL-10 inhibitory effect.<br />

(3) Tumors express FasL and induce apoptosis of effector T cells. Small interfering RNA (siRNA) can be used to<br />

knock-down Fas receptor in specific CTL, allowing a significant reduction of their susceptibility to Fas/FasL-<br />

mediated apoptosis.

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