Herein, we validated the superior inhibitory potency of second-generation sgp130FlyRFc using an IL-6-dependent lymphoma cell line and xenograft tumor model and established a proof-of-concept gene therapeutic approach for sustained intratumoral delivery of anti-cytokine therapeutics, that can serve as an alternative for scaled-up manufacturing and repeated systemic administration. The gene discussed is IL6; the disease is neoplasm.