Heat shock proteins gp96 as immunogens in cancer patients

Abstract

Heat shock proteins have been the focus of many experimental studies during the last few years in order to understand their biology and their imunologic features. We conducted pre-clinical experiments showing that gp96 purified from human melanoma lines can represent melanoma antigens and stimulate T cells known to recognize such antigens. Clinical studies of vaccination were then initiated by our group by using heat-shock protein gp96 purified from autologous tumor tissues in patients with melanoma and colorectal carcinoma. The results of these trials in metastatic melanoma patients with measurable disease showed that a melanoma-specific T cell response can be generated or increased in approximately 50% of vaccinated patients. Moreover, signs of clinical responses were obtained consisting of two complete responses and three long-lasting stabilizations. Similar results were obtained in patients with liver metastases of colorectal cancer made disease-free by surgery. In both studies a clear association was found between T cell immune response induced by the vaccine and clinical response both in the trial of melanoma (tumor response) and in that of colorectal cancer patients (disease-free and overall survival at 5 years).

Proteomics of the Radioresistant Phenotype in Head-and-Neck Cancer: Gp96 as a Novel Prediction Marker and Sensitizing Target for Radiotherapy

“…By contrast, Gp96 can activate immunity and cause an antitumor response through the formation of stable complexes with tumor-derived antigenic peptides and cross-presentation of antigenic peptides onto major Histocompatibility Complex class I-restricted epitopes, which activates T cells (27). Therefore, Gp96 peptide is currently being evaluated as a therapeutic vaccine for tumors (28).…”

A Heat Shock Protein 70-Based Vaccine with Enhanced Immunogenicity for Clinical Use

“…Importantly, immunization of mice with HSP.PC provides protection against the challenge with the tumor cells from which HSP.PC are purified or slows the progression of that tumor (7, 10, 31). Based on these results, HSP-based vaccines have been used in human clinical trials (12–16, 32–34). In the early phase I and/or II trials with GP96.PC (vitespen) purified from patient-derived tumors, immunologic and clinical responses were obtained in a subset of patients with malignant tumors (12, 13, 15, 32).…”

Expression and its clinical significance of heat shock protein gp96 in human osteosarcoma

“…The HSPgp96 molecules that were purified from tumor tissues may present peptides associated with them to major histocompatibility complex (MHC, or HLA in human) class I molecules for recognition by cytotoxic T lymphocytes (CTL) and thereby elicit protective and therapeutic cellular immune responses [17][18][19]. Parmiani et al found that the tumor vaccine made up of the HSPgp96 purified from the colorectal cancer patient can improved the T cell-mediated immunity reaction by 50% [20]. HSPgp96 which is the effective activating factor in the innate immunity can activate the IL-12 and dendritic cell (DC) [21,22], and could made the DC matured by means of activating the production of pro-inflammatory factor and of transmitting signal through Toll-like receptor-2 and receptor-4.…”