TIMP2 or arginine deprivation localized to the melanoma tumor cell environment by the treatment with TIMP2- or PADI1-expressing oncolytic adenoviruses (ONCOS-209, ONCOS-210, and ONCOS-212) exhibited similar reduction of weight gain as the vehicle-treated group, suggesting the possibility of minimal systemic toxicity. The gene discussed is PADI1; the disease is melanoma.