Vaccination with Autologous Tumor-derived Heat-Shock Protein Gp96

Heat-shock protein gp96 taken from a patient’s tumor and reapplied to the individual as an autologous vaccine enables the specific activation and expansion of effective cytolytic and helper T-cell effector functions through cross presentation of bound tumor antigens on MHC Class-I and Class-II molecules. Creative Biolabs is a world leader in the field of cancer vaccine development and our laboratory has been dedicated to the development of the autologous tumor-derived gp96-based vaccine that generates effective anti-tumor immunity. With our extensive experience and advanced platform, we are therefore confident in offering the best development services for heat-shock protein-based vaccines.

Heat-Shock Protein Gp96

Heat shock protein gp96 is a highly conserved and monomorphic glycoprotein in the endoplasmic reticulum, which functions as molecular chaperone and can associate with a variety of antigenic peptides noncovalently in vivo and in vitro. Gp96 purified from tumors is able to initiate efficient tumor specific CTL responses and protective immunity. Recent studies have shown that gp96 molecules are involved in the major histocompatibility complex class I-restricted antigen presentation pathway. Antigenic peptides derived from viral, tumor, mycobacterial, and minor histocompatibility antigens have been isolated from Gp96 and identified. Immunization of mice with gp96 preparations isolated from cancer cells can elicit a cancer-specific protective T cell immune response that is recallable, which is a prerequisite for gp96 as a therapeutic vaccine against cancers. The immunogenicity of gp96 molecules is due to the antigenic peptides associated with them. These phenomena provide a new possibility for cancer immunotherapy.

Fig.1 Role of heat shock proteins in cancer: Heat shock proteins (e.g., gp96) stimulating anticancer immunity. (Nutan T. 2015)

The Development of Vaccination with Autologous Tumor-derived Heat-Shock Protein Gp96

Molecular chaperone–peptide complexes extracted from tumors have been intensively studied. Heat shock protein (HSP) vaccines have been proved to be effective and safe in treating a number of cancers. Notably glycoprotein (Gp) 96, are of special interest, because they can obtain molecular peptide-fingerprints of the protein array characteristic for a particular cell. Association of Gp96 with peptides has been shown to be essential for cross-presentation and activation of T cells. Therefore, Gp96-peptide complexes extracted from cancer cells has tumor-specific peptides and are immunogenic, thus providing a tool for active immunization against the tumor.

The clinical application of Gp96–peptide preparations as anticancer vaccine has been studied in several Phase I/II/III trials in patients with various types of malignancies:

Creative Biolabs’ Gp96-Peptide Complex Vaccine

Our laboratory has been dedicated to the development of the autologous tumor-derived gp96-based vaccine that generates effective anti-tumor immunity. HSP vaccines in their purest form are prepared by purification of Gp96 peptide complexes from patients and deploying them in immunotherapy in an autologous mode. Vaccination with gp96 may serve as a potent modality to induce both systemic and mucosal immunity. Such method utilizes the combined adjuvant and antigen delivery capacity of gp96 to generate cytotoxic immunity against various antigens in anti-cancer vaccination.

Features

• Improved immunogenicity. Gp96 binds a broad range of immunogenic peptides without MHC-haplotype restrictions. The immunological properties of Gp96 derive from noncovalently associated peptides as well as from its intrinsic immunostimulatory adjuvant capacity.
• Safety. This approach appears to be relatively safe in cancer therapy as indicated by Phase I and II clinical trials.
• Well-tolerated. Autologous gp96 vaccine treatment is related to mostly weak and very limited side effects, which seems to be a well-tolerated therapeutic option.
• Personalized therapy. Optimal vaccines would be individualized and built around the antigenic repertoire of the individual patient. Gp96 taken from a patient’s tumor and reapplied to the individual as an autologous vaccine enables the specific activation and expansion of effective cytolytic and helper T-cell effector functions through cross-presentation of bound tumor antigens on MHC Class-I and Class-II molecules.

Creative Biolabs offers first-class customizable vaccine development services to clients globally. Contact our scientists to discuss your project in details and experience our expert services.

Reference

1. Nutan, Tyagi. (2015). “The wonderous chaperones: A highlight on therapeutics of cancer and potentially malignant disorders.” Journal of Oral and Maxillofacial Pathology. 19(2): 212.

All of our products can only be used for research purposes. These vaccine ingredients CANNOT be used directly on humans or animals.