The clinical course of in situ Ad-REIC is summarized in Figure 1. Ad-REIC (1.0 × 1012 vp/1.2 mL) was directly injected into the left obturator LN (more than 30 mL in volume) under CT guidance. After two scheduled injections, a significant decrease in serum PSA level (31.27→56.08→17.23 ng/mL) and almost complete necrosis within the injected LN was observed by CT and histological examinations (Fig. 2B). Notably, similar remarkable necrotic changes were also seen in other noninjected metastatic pelvic LNs. Based on these clinical findings, an additional four Ad-REIC injections were administered (Fig. 2C), leading to complete control of pelvic LNs with further PSA decline (5.02 ng/mL), as shown in Figures 1 and 3. On the other hand, newly developed mul­tiple para-aortic LNs metastases progressed with gradual PSA re-elevation (17.15 ng/mL). Next, additional six Ad-REIC injections were administered into para-aortic metastatic LNs (Figs. 1 and 4), resulting in remarkable PSA decline (2.57 ng/mL), and necrotic changes in the targeted LNs were detected by CT and histological examination (Fig. 5). Consequently, the patient was treated successfully for one year by 12 injections at an average four weeks’ interval. In the following year, three therapeutic Ad-REIC injections were administered into newly enlarged, gourd-shaped left para-aortic LNs, after a biopsy specimen from the upper part of the left para-aortic LNs showed clusters of viable cancer cells (Fig. 6A). Two injections into the upper part and one into lower part of the LNs resulted in adequate control of the whole of the metastatic LNs (Figs. 3 and 6B) with PSA decline (2.25 ng/mL). No bone or visceral metastases and no par­ticular adverse events including immune-related response were observed, besides mild transient fever associated with 15 Ad-REIC injections during the 24-month treatment period.

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