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Cancer Vaccine - AntigenicsHeat-Shock Protein Cancer Vaccine - Antigenics, HSPPC-96, Oncophage®

 

作者: &NA;,  

 

期刊: BioDrugs  (ADIS Available online 2002)
卷期: Volume 16, issue 1  

页码: 72-74

 

ISSN:1173-8804

 

年代: 2002

 

出版商: ADIS

 

关键词: Cancer vaccine HSP, pharmacodynamics;Research and development;Vaccines, pharmacodynamics

 

数据来源: ADIS

 

摘要:

Antigenics is developing a therapeutic cancer vaccine based on heat-shock proteins (HSPs)1. The vaccine [HSPPC-96, Oncophage®] is in a pivotal phase III clinical trial for renal cancer at 80 clinical sites worldwide. The trial is enrolling at least 500 patients who are randomised to receive surgical removal of the primary tumour followed by out-patient treatment with Oncophage®or surgery only. This study was initiated on the basis of results from a pilot phase I/II study and preliminary results from a phase II study in patients with renal cell cancer. In October 2001, Oncophage®was designated as a fast-track product by the Food and Drug Administration in the US for the treatment of renal cell carcinoma.Oncophage®is in phase I/II trials in Italy for colorectal cancer (30 patients) and melanoma. The trials in Italy are being conducted at the Istituto dei Tumouri, Milan (in association with Sigma-Tau). Preliminary data from the phase II trial for melanoma was presented at the AACR-NCI-EORTC International Conference in Florida, USA, in October 2001.Oncophage®is also in a phase I/II (42 patients) and a phase II trial (84 patients) in the US for renal cell cancer, a phase II trial in the US for non-Hodgkin’s lymphoma (35 patients), a phase II trial in the US for sarcoma (20-35 patients), a phase I/II trial in the US for melanoma (36 patients), and phase I/II trials in Germany for gastric (30 patients) and pancreatic cancers. A pilot phase I trial in patients with pancreatic cancer began in the US in 1997 with 5 patients enrolled. In November 2000, Antigenics announced that this trial had been expanded to a phase I/II study which would now include survival as an endpoint and would enroll 5 additional patients. The US trials are being performed at Memorial Sloan-Kettering Cancer Center and the M.D. Anderson Cancer Center. The trials in Germany are being carried out at Johannes Gutenberg-University Hospital, Mainz.Oncophage®is an autologous vaccine consisting of purified complexes of tumour-derived HSPs linked to tumour antigen peptides. When these HSPPC are readministered to a patient following surgery or biopsy of the tumour, the antigenic tumour peptides are expressed on the surface of potent antigen-presenting cells of the immune system, such as macrophages and dendritic cells. This stimulates a much more powerful anti-tumour immune response than that generated by expression of the same antigens by the tumour cell. Thus, Antigenics autologous HSP technology is attractive because it is highly specific for individual patients and circumvents the need for identification of specific antigens for individual cancers (i.e. it does not require definition of the antigenic epitopes on cancer cells) and it overcomes the immune tolerance associated with various tumours. Oncophage®is manufactured in a 10-hour process from surgically resected autologous tumour. A minimum of 1-3g of tumour tissue is required to produce enough Oncophage®for a course of treatment. The major limiting factor for producing Oncophage®from a particular cancer is the ability to purify HSP from that cancer. From clinical studies to date, Antigenics has been able to produce HSP from 100, 98, 90, 71 and 30% of colorectal carcinoma, renal cell carcinoma, melanoma, gastric cancer and pancreatic cancer tumours, respectively. The low success rate with pancreatic cancers is because of the high concentration of proteases in that tissue type.HSPs are a family of highly conserved proteins present in the cells of all organisms. They function as molecular chaperones, assisting the correct folding of polypeptides and aiding intracellular protein transport. In addition, HSPs associate with a broad range of peptides derived from intracellular protein degradation, including antigenic peptides produced in tumour cells.Antigenics has exclusively licensed worldwide rights to its HSP immunotherapeutic complexes from Mount Sinai School of Medicine and Fordham University in the USA. On 3 November 1998, Antigenics was issued a US patent (5,830,464) covering immunotherapy in which antigen-presenting cells are isolated and mixed with heat shock protein-antigen complexes purified from patients’ tumours. The patent was issued to Fordham University, New York, US, who subsequently licensed it to Antigenics.Antigenics has an agreement with Sigma Tau, under the terms of which the latter company will fund 2 clinical trials in return for an option to market Oncophage®in Italy, Portugal, Spain and Switzerland. Antigenics also has an agreement with Medison for marketing of Oncophage®in Israel.

 

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