Chimeric cell-targeting pathogenic organism and method of...

Chemistry: molecular biology and microbiology – Micro-organism – per se ; compositions thereof; proces of... – Bacteria or actinomycetales; media therefor

Reexamination Certificate

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C435S254100, C435S254220

Reexamination Certificate

active

06929941

ABSTRACT:
The invention chimeric organism comprises a chimeric surface integrin-like fusion protein in which the I domain has been replaced by an antibody fragment that binds a disease-associated antigen on a cell. Binding of the antibody fragment to the disease-associated antigen triggers virulent transformation of the chimeric pathogenic organism so as to cause the organism to infiltrate the target cell with specificity. Preferably, the chimeric organism is a chimeric pathogenicC. albicanshaving an INT1 fusion protein in which the I domain is replaced by an antibody fragment, preferably a single chain antibody, and in which expression of an iron transporter gene necessary for infiltration of a target cell is triggered under the control of a EFG1p response element. Binding of the antibody to the disease-associated antigen causes filamentous transformation in the chimeric pathogenicC. albicansand specific infiltration of target cells. The invention chimeric pathogenic organisms are used in therapeutic methods to specifically infiltrate and destroy diseased cells to which the antibody fragment binds while remaining non-pathogenic to normal cells.

REFERENCES:
patent: 6083751 (2000-07-01), Feldhaus et al.
patent: 6346411 (2002-02-01), Hostetter et al.
Lo et al (Mol. Biol. Cell vol. 9, pp 161-171, 1998).
Gale et al., “Linkage of Adhesion, Filamentous Growth, and Virulence inCandida albicansto Single Gene,INT1,” Science, 279:1355-1358 (1998).
Moritz et al., “Cytotoxic T lymphocytes with a grafted recognition specificity for ERBB2-expressing tumor cells,”Proc. Natl. Acad. Sci. USA, 91:4318-4322 (1994).
Wels et al., “Biotechnological and gene therapeutic strategies in cancer treatment,”Gene159:73-80 (1995).
Calderone et al., “Adherence and Receptor Relationships ofCandida albicans”, Microbiol. Rev., 55(1):1-20 (1991).
Gale et al., “Linkage of Adhesion, Filamentous Growth, and Virulence inCandida albicansto a Single Gene,INT1,” Science, 279:1355-1358 (1998).
Moritz et al., “Cytotoxic T lymphocytes with a grafted recognition specificity for ERBB2-expressing tumor cells,”Proc. Natl. Acad. Sci. USA, 91:4318-4322 (1994).
Wels et al., “Biotechnological and gene therapeutic strategies in cancer treatment,”Gene159:73-80 (1995).
Sonneborn et al., “Control of White-Opaque Phenotypic Switching inCandida albicansby the Efg1p Morphogenetic Regulator”,Infect. Immun., 67(9):4655-4660 (1999).

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