Abstract
RB-94 is a truncated form of the RB tumor suppressor gene which has shown marked cytotoxicity in every human tumor type tested to date without affecting normal cells. A systemically administered, tumor-targeted nanocomplex for systemic gene delivery (termed SGT) has been developed. In the SGT nanocomplex, the payload is encapsulated within a cationic liposome. The surface of the liposome is decorated with an anti-transferrin receptor (TfR) single chain antibody fragment (scFv) designed to target cancer cells by binding to the TfR which is highly expressed on tumor cells. Here we describe the results of a DNA dose escalating first-in-man Phase l study of SGT encapsulated RB-94 (SGT-94) for the treatment of metastatic genitourinary tumors. The majority of the cancers treated in this study were bladder cancers. Treatment with SGT-94 was well tolerated with minimal side effects observed. Moreover, among the 11 evaluable patients of 13 treated, a complete remission (CR) in a lung metastasis, two partial remissions (PRs) and three incidences of stable disease (SD) were observed. The CR and PRs occurred at the highest dose (2.4 mg DNA) tested. In addition, there is strong evidence for tumor-specific targeting including data from two resected lung metastases. In these metastatic lesions, the presence of RB94 was documented by both PCR and Western blotting in the tumors. However, RB94 was absent in contiguous normal lung tissue. Therefore, this Phase I study demonstrates not only the safety, but also the anti-cancer potential of the SGT-94 nanocomplex and suggests that additional studies using SGT-94 alone or in combination with chemotherapy, radiation or other modalities are warranted.
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