Co-Administration of Vadimezan and Recombinant Coagulase-NGR Inhibits Growth of Melanoma Tumor in Mice

Tumor vascular targeting (TVT) appeared as an appealing approach to fight cancer, though, the results from the clinical trials and drugs in the market were proved otherwise. The promise of anti-angiogenic therapy as the leading TVT strategy was negatively affected by the discovery that tumor vascularization can occur non-angiogenic mechanisms such as co-option. An additional strategy is the induction of tumor vascular infarction and ischemia. Such that we used truncated coagulase (tCoa) coupled with tumor endothelial targeting moieties to produce tCoa-NGR fusion proteins. We showed that tCoa-NGR can bypass coagulation cascade to induce selective vascular thrombosis and infarction of mild and highly proliferative solid tumors in mice. Moreover, combination therapy can be used to improve the potential of cancer vascular targeting modalities. Herein, we report a combination of tCoa-NGR with the vascular disrupting agent, Vadimezan. Our results show that the synergistic work of these two agents can significantly suppress the growth of B16-F10 melanoma tumors in C57/BL6 mice. For the first time, we used the simultaneous benefits of two strategies for inducing thrombosis and the destruction of tumor vasculature as spatial co-operation. The tCoa-NGR induces thrombosis which reduces blood flow in the peripheral tumor region. And combined with the action of Vadimezan, which targets inner tumor mass, growth and proliferation of melanoma tumors can be significantly suppressed.