Stimulation of cell-mediated immune responses by targeted particulate genetic immunization
OwnerLouis D. Falo JR., Kenneth L. Rockinventors
Life of this patent
Estimating the term…
Abstract
The present invention relates to various methods of genetic immunization for the purpose of providing antigen-specific immunity in a mammalian host, including a human host. The invention is based on the ability to direct particulate polynucleotides which express an antigenic protein or protein fragment to the cytoplasm of host target cells, such as antigen presenting cells. A directed delivery of such particulate polynucleotides to the cytoplasm of antigen presenting cells will stimulate antigen-specific CTL production, thus promoting destruction of affected cells such as neoplastic cells and virally infected cells.
Claims67
An in vivo method of therapeutic or prophylactic genetic immunization of a mammalian host, which comprises:
- (a) generating a DNA fragment which expresses an antigenic protein or antigenic protein fragment;
- (b) distributing said DNA fragment on a particle surface, resulting in a particulate polynucleotide;
- (c) inoculating said mammalian host with said particulate polynucleotide;
- and,
- (d) delivering said particulate polynucleotide to the cytoplasm of a target cell within said mammalian host, such that said expressed antigenic protein or antigenic protein fragment is presented to the membrane surface of said target cell through the MHC class I pathway.
The method of claim S wherein said viral antigen is Hepatitis B surface antigen.
An in vivo method of therapeutic or prophylactic genetic immunization of a mammalian host, which comprises:
- (a) generating a DNA fragment which expresses an antigenic protein or antigenic protein fragment;
- (b) distributing said DNA fragment on a particle surface, resulting in a particulate polynucleotide;
- (c) inoculating said mammalian host with said particulate polynucleotide using a biolistic device;
- and,
- (d) delivering said particulate polynucleotide to the cytoplasm of a target cell within said mammalian host, such that said expressed antigenic protein or antigenic protein fragment is presented to the membrane surface of said target cell through the MHC class I pathway.
An in vivo method of therapeutic or prophylactic genetic immunization of a mammalian host, which comprises:
- (a) generating a DNA fragment which expresses an antigenic protein or antigenic protein fragment;
- (b) distributing said DNA fragment on a particle surface, resulting in a particulate polynucleotide;
- (c) inoculating said mammalian host with said particulate polynucleotide by direct injection;
- and,
- (d) delivering said particulate polynucleotide to the cytoplasm of a target cell within said mammalian host, such that said expressed antigenic protein or antigenic protein fragment is presented to the membrane surface of said target cell through the MHC class I pathway.
An ex vivo method of therapeutic or prophylactic genetic immunization of a mammalian host, which comprises:
- (a) generating a DNA fragment which expresses an antigenic protein or antigenic protein fragment;
- (b) distributing said DNA fragment on a particle surface, resulting in a particulate polynucleotide;
- (c) delivering said particulate polynucleotide to the cytoplasm of a target cell of a mammalian host in vitro, such that said expressed antigenic protein or antigenic protein fragment is presented on the membrane surface of said target cell through the MHC class I pathway;
- and,
- (d) inoculating said mammalian host with said target cell by direct injection.
An ex vivo method of therapeutic or prophylactic genetic immunization of a mammalian host, which comprises:
- (a) generating a DNA fragment(s) which express a molecule which enhances the antigen presentation function of an APC;
- (b) distributing said DNA fragment(s) on a particle surface, resulting in a particulate polynucleotide;
- (c) delivering said particulate polynucleotide to the cytoplasm of a target cell of a mammalian host in vitro, such that said expressed antigen presentation enhancing protein or proteins is expressed in a biologically significant form and at biologically significant levels;
- (d) inoculating said mammalian host with said target cell by direct injection.
Dependencies are inferred from the claim text.