The present invention describes a unique method of treating cancer with the administration of an improved DAGRS™ construct which functions as a humanized agent specifically targeting cancer cells in vivo. A specific DAGRS™ is described constructed of a humanized drug delivery biologic, carboxyl to an Apoptin fragment consisting of Apoptin's proline-rich SH3-binding fragment, a spacer, and a MAP kinase (MAPK) phosphorylation site, in replacement of the SH3-binding domain at HIV-1 TAT's amino terminus. Apoptin is a viral protein with incumbent immunogenicity and toxicity in humans. Improved DAGRS™ constructs are described that replace the viral VP3 peptide with human AKT peptide or derivative, all equivalently spaced 11 amino acids from the initial proline to the beginning of the MAPK phosphorylation site, through which technology the DAGRS™ is fully humanized. DAGRS™ provide for improved bioavailability, enhanced specific activity, and low toxicity for in vivo treatment of cancer. DAGRS™ are a superior method for targeting any oncogene with an inhibitory peptide. An algorithm for “humanization” is described through which human functional equivalent(s) to viral product(s) are identified by alignment of peptides anchored at each end by matching functional motifs that are spaced equivalently distant in the two aligned peptides. The algorithm totally disregards the primary amino acid composition of the spacer, and as such separates from current computer algorithms that prioritize primary amino acid alignments. Accounting for spacing dictates that functional domains be oriented correctly in three dimensions. The invention taught here can be developed into computer algorithms for rapidly identifying these anchored alignments, and thereafter developing safe humanized drugs from disruptive viral activities. Computers once taught the basic rules for anchoring equivalents, can improve on the basic algorithm through artificial intelligence to expand drug development.

The present invention discloses an in-vitro method for transferring biological material into activated NK cells with a pseudotyped retroviral vector particle or a virus-like particle thereof, comprising the steps a) activation of NK cells, and b) addition of said pseudotyped retroviral vector particle or virus-like particle thereof to said activated NK cells, wherein said pseudotyped retroviral vector particle or virus-like particle thereof comprises a modified baboon endogenous retrovirus (BaEV) envelope glycoprotein that is able of binding to and fusing with a hematopoietic cell membrane, thereby transferring biological material into said activated NK cells. Preferentially, the activating of NK cells is performed by the addition of a IL-1 family cytokine to the NK cells.

Compositions and methods for targeted treatment of cancer are disclosed. In particular, the invention relates to methods of targeting anti-cancer therapy to cells exhibiting aberrant signaling associated with cancer pathogenesis by administering synthetic signaling proteins that couple detection of an oncogenic signal to release of therapeutic agents into cancerous cells.

The present invention discloses an in-vitro method for transferring biological material into activated NK cells with a pseudotyped retroviral vector particle or a virus-like particle thereof, comprising the steps a) activation of NK cells, and b) addition of said pseudotyped retroviral vector particle or virus-like particle thereof to said activated NK cells, wherein said pseudotyped retroviral vector particle or virus-like particle thereof comprises a modified baboon endogenous retrovirus (BaEV) envelope glycoprotein that is able of binding to and fusing with a hematopoietic cell membrane, thereby transferring biological material into said activated NK cells. Preferentially, the activating of NK cells is performed by the addition of a IL-1 family cytokine to the NK cells.

Compositions and methods for targeted treatment of cancer are disclosed. In particular, the invention relates to methods of targeting anti-cancer therapy to cells exhibiting aberrant signaling associated with cancer pathogenesis by administering synthetic signaling proteins that couple detection of an oncogenic signal to release of therapeutic agents into cancerous cells.

The present inventors successfully introduced genes into stem cells of airway epithelial tissues using simian immunodeficiency virus vectors pseudotyped with F and HN, which are envelope glycoproteins of Sendai virus. Gene transfer into airway epithelial tissue stem cells using a vector of the present invention is useful for gene therapy of genetic respiratory diseases such as cystic fibrosis. Furthermore, it is possible to select respiratory organs such as the lungs as production tissues for providing proteins that are deficient due to genetic diseases.

Disclosed are methods for manipulating and expanding stem cell populations, including adult stem cells, the cells produced by such methods, and various protein constructs related thereto.

The present invention describes unique means for reducing autoreactivity that sensitizes against sustained treatments, and toxicity associated with administration of biologicals, in order to develop safer cancer immunotherapeutics. Short functional sequences are identified in the biologic and matched to their most homologous human counterpart. The human homologs are swapped in to replace their foreign counterparts. Alternatively, variants are selected that have exhibit less toxicity in human or primate experiments from nature, and these sequences are swapped in to replace their counterparts in the biologic. Also, human sequences that mediate the same function as foreign sequences in the biologic, but lack any sequence homology, can be swapped in for their foreign sequence counterparts. These inventions are applied to derivatize the HIV/SIV Tat protein into humanized trimers (CATS) useful for the treatment of cancer.

The present inventors successfully introduced genes into stem cells of airway epithelial tissues using simian immunodeficiency virus vectors pseudotyped with F and HN, which are envelope glycoproteins of Sendai virus. Gene transfer into airway epithelial tissue stem cells using a vector of the present invention is useful for gene therapy of genetic respiratory diseases such as cystic fibrosis. Furthermore, it is possible to select respiratory organs such as the lungs as production tissues for providing proteins that are deficient due to genetic diseases.

The present invention relates to a new vaccine delivery system. In particular, the present invention includes compositions and methods of integrally transformed non-pathogenic, commensal bacteria that can express a nucleic acid molecule of a foreign polypeptide, wherein the nucleic acid molecule that encodes the foreign polypeptide is stably integrated into genomic DNA of the bacteria. The foreign polypeptide includes a vaccine antigen that elicits an immunogenic response, an inhibitor of a pathogen, or an immune booster or modulator.