Operationally unsaturated ruthenium complex stabilized by a phosphine 1-azaallyl ligand.

Coordinatively unsaturated transition-metal compounds stabilized by supplemental electron donation from π-basic ligands are described as "operationally unsaturated". Such complexes are useful analogues of active catalyst structures that readily react with substrate molecules. We report that [Ph2P(C6H4)NCHC(CH3)2]- (L1) effectively stabilizes Ru(II) in an operationally unsaturated form. In the absence of Lewis bases, the 1-azaallyl group of L1 dominantly coordinates through a κ1-N mode, but can readily and reversibly isomerize to an η3-NCC coordination mode to stabilize the metal. As an operationally unsaturated complex, Ru(Cp*)(L1) dimerizes at low temperature. At ambient temperature it rapidly reacts with pyridine or PPh3 to form an adduct. These findings with L1 demonstrate that changes in the hapticity of a 1-azaallyl fragment offer an alternative means to stabilize low-coordinate metals.

Efficient transfer of PSA and PSMA cDNAs into DCs generates antibody and T cell antitumor responses in vivo.

Gene therapy for prostate cancer may be realized through transduction of whole genes, such as PSA or PSMA, into immunotherapeutic dendritic cells (DCs). An oncoretroviral vector encoding human PSMA and a bicistronic oncoretroviral vector encoding human PSA and cell surface CD25 cDNAs were constructed. Remarkably, transfer of PSA/CD25 or PSMA cDNA during murine hematopoietic cell differentiation into DCs occurred with approximately 80% efficiency. In vitro, transduced DCs retained allostimulatory function and primed syngeneic T cells for tumor antigen-specific IFN-gamma secretion. In test experiments designed to elucidate mechanisms in vivo, syngeneic recipients of transduced DCs had increased anti-human PSA antibody titers and tumor-specific CD8(+) T cell IFN-gamma secretion with no detectable immune response to CD25. Gene-modified DC recipients had increased protection from specific tumor challenge for at least 18 weeks post-vaccination. DC vaccination also protected both male and female recipients. Gene-modified DC vaccination mediated regression of established, specific gene-expressing, TRAMP-C1 prostate cancer cell tumors. These findings indicate that antibody and cellular responses generated through PSA and PSMA gene transfer into DC yielded protective immunity, thereby providing further preclinical support for the implementation of immuno-gene therapy approaches for prostate cancer.