HSP Vaccines on the Fast Track

Personalized approach likely to be applicable to most types of human cancers

In October 2001, the US Food and Drug Administration (FDA) assigned Fast Track Product designation to Antigenics’ Oncophage® cancer vaccine for the treatment of renal cell carcinoma. Oncophage is the first personalized cancer product to be granted this status, and is one of a series of products under development based on Antigenics’ proprietary heat shock protein technology. Heat shock proteins are ubiquitous in human biology and have multiple functions. One of their central, most fundamental functions is in the immune system - they function as chaperones for all peptides that are transported through the endoplasmic reticulum and loaded onto MHC molecules. In addition, they are key regulators of dendritic cell function, being one of the most powerful ‘on-switches’ for dendritic cell maturation, migration and antigen processing. These multiple functions for heat shock proteins within the immune system have given rise to their being described as the ‘Swiss army knife’ of the immune system.

Dr Jonathan Lewis, Antigenics’ Chief Medical Officer, an oncologist and clinical immunologist who formerly practised within the Memorial Sloan-Kettering Cancer Center, outlined to Phacilitate the importance of this development in the context of the company’s technology platform and product pipeline.

Dr Lewis explained, "At Antigenics we have developed heat shock protein technology both to treat cancer and infectious disease. Because of the unique DNA and molecular profile of each human cancer, we have implemented an autologous/personalized approach to cancer vaccination. This utilizes the chaperone function of heat shock proteins, constructing a vaccine that has the entire repertoire of peptide antigens for that particular cancer in that particular patient. To date we have shown promising results in renal cell cancer, melanoma, pancreatic cancer and colorectal cancer." On the other hand, Lewis points out, for infectious disease an ‘off the shelf’ approach is sufficient. Antigenics have initiated an infectious disease program utilizing recombinant HSP70 together with a cognate peptide for HSV-2 (genital herpes). The heat shock protein acts as a powerful ‘on switch’ for dendritic cells, and as an adjuvant to T cells.

Oncophage is an autologous tumor-derived gp96 heat shock protein-peptide complex. Lewis believes that compelling reasons for the FDA’s decision to assign Fast Track status were the promising clinical results in multiple Phase II studies and virtual absence of side affects. In the context of a real need for new more effective and less toxic treatments for the overwhelming majority of cancers, the importance of this approach was clear. In the light of the new designation, and subject to approval, Antigenics hope to commercialize Oncophage in 2004.

The individualized treatment procedure is simple and seamless to both patient and physician. Following operation and resection, a small portion of the tumor is packed in simple modular containers and shipped to Antigenics R&D and manufacturing facility in Woburn, MA, USA. The team then manufactures an autologous gp96 heat shock protein peptide complex vaccine (Oncophage) in approximately 10 hours. On completion of quality control procedures, the vaccine is shipped in solution in vials to the hospital of origin in approximately two weeks. When the patient is ready for vaccination, the vial is taken from the pharmacy to the clinic and the solution is injected into the skin of the patient. Lewis points out that the procedure is an outpatient treatment, with no side affects and excellent quality of life outcomes.

In the longer term, Lewis expects the treatment to have applications across a much wider range of indications. "We are currently focused on renal cell cancer because it is the furthest along in our development program. Very close behind is melanoma, and we are about to start two pivotal trials in this indication. We certainly do anticipate a wider range of indications for the vaccine, likely to include most cancers. Our development continues on a broad front in solid tumors and will expand into liquid tumors like leukemia in the near future", he said.

Although the treatment involves a personalized approach, the cost of treatment is anticipated to be very similar to that of other current new cancer therapies, such as Genentech’s Herceptin® (trastuzumab). Lewis says, "Given this, together with the fact that Oncophage will be delivered as an outpatient monotherapy, we do not see any barriers to successful commercialization".

In November, Antigenics announced the roll out of trials of AG-702 for use in the treatment of genital herpes. AG-702 is an ‘off the shelf’ vaccine that is recombinant HSP-70 together with a cognate peptide from HSV-2. Lewis believes that the prospects for expansion of HSP technology into the infectious diseases field are excellent. He says, "This is our first infectious disease trial. We will be expanding the same technology in the pre-clinic and clinic in both genital herpes and several other diseases in the near future. We also expect this ‘off the shelf’ approach to be applicable both in the preventive and therapeutic setting".

As for the future, Lewis predicts that HSP technology will be broadly applicable in the development of therapeutic vaccines. He says, "The molecular and cell biology underlying this technology is one of the most fundamental processes throughout all of biology, including even invertebrates and even unicellular organisms. The same biology occurs in all cancer cells. We therefore anticipate that this approach will likely be applicable to most types of human cancers. Furthermore, it will also be applicable to many different kinds of serious infections and will have a role in treating certain autoimmune diseases".

© Phacilitate Ltd 2006