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12:00 AM
 | 
May 29, 2006
 |  BioCentury  |  Product Development

Antigen picking strategies

Cautious Optimism

Antigen picking strategies

While developers of cancer vaccines now have a much clearer picture of the setting for prosecuting the immune response, what remains unresolved is "who" should choose the target antigens - the drug or the patient's immune system.

One possibility is that the vaccine contains a non-patient-specific antigen, or multiple antigens; the body then reacts against them, and the patient has a clinical response. Another strategy is to use antigen(s) derived from the individual patient's tumor, which the body then reacts against by virtue of the vaccine.

A third possibility is that a vaccine containing a non-patient-specific antigen creates an initial immune response that ultimately leads the patient's immune system to react against the patient's own tumor antigens.

This issue is likely to be resolved empirically, and it may turn out that all three strategies work as long as the antigens are provided in the right context. The answer also may depend on the type of cancer.

The patient rules

On one end of the spectrum are companies taking the patient-specific approach, like Antigenics Inc. (AGEN, New York, N.Y.).

"In the last four years, we have learned that cancers of individuals do have their own profiles," said Chairman and CEO Garo Armen. "If so, it stands to reason that to get the appropriate immune response, you need to recognize that cancer's individuality. We are not picking the antigen for the patients. We are entirely using the antigen repertoire of the patient's cancer."

AGEN's Oncophage vitespen uses heat shock protein gp96 and associated peptides isolated from the patient's tumor. The idea is that the chaperone protein Hsp96 carries with it the properly processed and antigenically relevant peptides from the tumor.

Preliminary analysis of a Phase III trial in Stage IV metastatic melanoma showed it missed the primary endpoint of overall survival. However, in a prospectively defined subset of patients with Stage M1a disease, median survival of treated patients was 20.9 months versus 12.8 months in the comparator arm(see BioCentury, Oct. 17, 2005).

Final data will be presented at ASCO, but the disappointing data from the company's renal cell carcinoma trial means that AGEN has had to scrap plans to submit a BLA for the RCC indication this year. AGEN plans to update its analysis of that trial in June.

MyVax from Genitope Corp. also is a patient-specific vaccine. It uses the idiotype protein from the patient's own tumor, combined with KLH (keyhole limpet hemocyanin carrier protein). Patients are also given GM-CSF. The KLH stimulates the innate immune system, while the GM-CSF helps activate dendritic cells.

Making such a vaccine is relatively straightforward in B cell cancers. Normal B cells each have a different antibody on their surface. If a B cell becomes malignant, each cell in the clone expresses the same antibody that was present on the parent cell. This antibody is the idiotype.

"Most other approaches are relatively non-specific," noted Dan Denney, founder, chairman and CEO of GTOP (Redwood City, Calif.). "The problem is that we don't know how many true targets there are for that patient's tumor - whether it's two or three or 15...

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