Cancer vaccine - vitespen
The expression of the heat shock proteins, or HSPs, in the body increases when cells are exposed to increased temperatures or other forms of stress. These molecular chaperones are also expressed under normal conditions, when they perform functions as part of the normal cell repair system, such as helping proteins to fold and transporting old proteins to be recycled.
The expression of the heat shock proteins, or HSPs, in the body increases when cells are exposed to increased temperatures or other forms of stress. These molecular chaperones are also expressed under normal conditions, when they perform functions as part of the normal cell repair system, such as helping proteins to fold and transporting old proteins to be recycled.
HSP-peptide complexes derived from tumour cells have potential as vaccines against cancer. One such complex, Vitespen, also known as Oncophage, is under development by US company Antigenics for use in several forms of cancer, although pancreatic and gastric tumours are not suitable. The vaccine is made from the patient's own tumour, and HSP can be isolated from numerous different tumours, including kidney, colorectal, lymphomas and melanomas.1
One of these is kidney cancer. In one trial in 84 patients with stage IV renal cell carcinoma undergoing nephrectomy, the vaccine was given either with or without interleukin-2, starting about four weeks after surgery.2 Subjects were given one injection for the first four weeks, then two injections at fortnightly intervals. Patients who achieved stable or responsive disease continued to be given injections of the vaccine, with four more doses at fortnightly intervals. Those whose disease had progressed were given four weeks of five-times-a-week doses of interleukin-2 on top of the four doses of vaccine. Those who had achieved a complete response after this time were given two more doses.
A total of 60 patients were evaluable, and two had a complete response, two a partial response and 33 progressed. The rest had either confirmed or unconfirmed stable disease. Those who had progressed on vaccine alone experienced stabilisation when IL-2 was added. Although it did not show a discernible benefit in most patients, using immunoregulatory agents as well may enhance its efficacy.
In another open label trial in kidney cancer patients, half of a group of 818 subjects were given vitespen, and the other half observation only, after nephrectomy.3 The vaccine was given once a week for four weeks, then every two weeks until the vaccine ran out. In the following two years, death rates and recurrence-free survival were only marginally better in the group given the vaccine; however, a potential improve-ment in recurrence-free survival in patients with early stage disease needs further validation.
It is also being investigated in melanoma. Of a total of 322 patients with stage IV melanoma, two-thirds were given vitespen and the remainder the physician's choice of treatment.4 The number of doses varied from 0 to 87, with a median of six. Exploratory landmark analyses show that patients who were in the M1a and M1b substages who received a larger number of injections survived longer than those who received fewer treatments. This distinction was not seen in patients in the M1c substage. Results suggest that patients who could receive at least 10 doses would be the candidate population for a confirmatory study.