Effective vaccination using in vitro peptide-loaded heat shock proteins, tumor-derived heat shock proteins, and heat shock-fusion proteins has been shown in viral, parasite, and tumor model systems. We demonstrate protective DNA-vaccination using gp96-peptide fusion proteins against the intracellular bacterial pathogen Listeria monocytogenes in a mouse model. In contrast to previous studies usi...

PURPOSE To develop effective immunotherapies for patients with multiple myeloma, it is important to use novel tumor antigens. Recent studies in solid tumors show that tumor-derived heat shock proteins (Hsp) can be used as immunogen; however, no such study has yet been reported in multiple myeloma. EXPERIMENTAL DESIGN We examined whether myeloma-derived Hsp gp96 can be used as a myeloma antige...

Heat shock protein (HSP) preparations derived from cancer cells and virus-infected cells have been shown previously to elicit cancer-specific or virus-specific immunity. The immunogenicity of HSP preparations has been attributed to peptides associated with the HSPs. The studies reported here demonstrate that immunogenic HSP-peptide complexes can also be reconstituted in vitro. The studies show ...

Exogenous antigens enter antigen-presenting cells through nonspecific mechanisms and are presented by the MHC II molecules. We show here that antigens chaperoned by the heat shock protein gp96 enter dendritic cells and B cells through a specific, CD91and LOX-1mediated mechanism, and are presented by MHC II molecules, in addition to MHC I molecules as previously demonstrated. Receptor utilizatio...

Given the aggressive spread of COVID-19-related deaths, there is an urgent public health need to support development vaccine candidates rapidly improve available control measures against SARS-CoV-2. To meet this need, we are leveraging our existing platform target Here, generated cellular heat shock chaperone protein, glycoprotein 96 (gp96), deliver SARS-CoV-2 protein S (spike) immune system an...

HSPPC-96 is a protein peptide complex consisting of a 96 kDa heat shock protein (Hsp), gp96, and an array of gp96-associated cellular peptides. Immunisation with HSPPC-96 induces T-cell specific immunity against these peptides; gp96 is not immunogenic per se. The non-covalent binding of gp96 to peptides is neither selective nor restricted to cell types. Thus, the collection of gp96-associated p...

The attenuated or non-pathogenic live vectors have been evolved specifically to deliver DNA into cells as efficient delivery tools in gene therapy. Recently, a non-pathogenic protozoan, Leishmania tarentolae (L.tar) has attracted a great attention. In current study, we used Leishmania expression system (LEXSY) for stable expression of HPV16 E7 linked to different mini-chaperones [N-/C-terminal ...

We recently have identified CD91 as a receptor for the heat shock protein gp96. CD91 was identified initially as a receptor for alpha(2)-macroglobulin (alpha(2)M). Gp96 and alpha(2)M are both ligands for CD91. Because gp96-chaperoned peptides can prime CD8(+) T cell responses and are re-presented by APCs, we tested alpha(2)M for similar properties. Our studies show that alpha(2)M binds peptides...

A number of Heat Shock Proteins (HSPs), in the extracellular environment, are immunogenic. Following cross-presentation of HSP-chaperoned peptides by CD91(+) antigen presenting cells (APCs), T cells are primed with specificity for the derivative antigen-bearing cell. Accordingly, tumor-derived HSPs are in clinical trials for cancer immunotherapy. We investigate the role of NK cells in gp96-medi...

Heat shock proteins (HSPs) such as gp96 are released from cells as a result of necrotic cell death. The ability of endogenous HSP-peptide complexes to elicit antigen-specific T cells requires representation of the chaperoned peptides by antigen-presenting cells. Re-presentation requires the uptake of HSP-peptide complexes through a receptor, suggested to be the low-density lipoprotein receptor-...