Finding that Immunoglobulin Isotypes Affect Efficacy
Dr. Schuster also pointed out that the real problem may relate to the way the recombinant vector was designed. “Both Favrille’s Specifid, expressed in an insect cell system, and Genitope’s MyVax, produced in CHO cells, were produced as recombinant proteins,” he said. “There is the potential that with recombinants, the three-dimensional conformation of the idiotype protein won’t be identical to the protein produced by the patient’s tumor.”
In the case of Genitope’s vaccine, the variable region of the patient’s idiotype was cloned into an IgG heavy-chain immunoglobulin. “Not all patients with FL produce IgG isotypes,” he explained.
“One possibility has been that the antibody isotype affects the body’s ability to mount an anti-idiotype immune response,” Dr. Schuster continued. “For example, IgG-bearing idiotype may be less immunogenic than IgM bearing idiotype.”
He further noted that data from the BiovaxID trial helped address this issue. “Because our vaccine was derived from the patient’s tumor, we had the idiotype and the isotype specific to the tumor. The recombinant studies all used IgG, one fundamental difference, while basically, in our trial, we used whatever a patient had.”
Dr. Schuster explained that in the BiovaxID trial, immunological and biochemical characterization showed that 55 patients’ tumors produced IgG isotype and 60 produced IgM isotype. “Among the IgG idiotypes, 40 got the IgG vaccine, and among IgM, 35 got the IgM vaccine. We could therefore look at disease-free survival in isotype-matched controls.
“Patients that got an IgM vaccine when compared to IgM controls showed a highly different disease-free survival, and basically, everybody in the study got an isotype-matched vaccine,” he added.
The investigators reported that in the IgM isotype group, they observed that patients who were treated with isotype-matched BiovaxID had significantly longer DFS: 52.9 months versus 28.7 months for patients who received the control vaccine. In contrast, in the IgG isotype group, there was no difference in median DFS between the patients who received isotype-matched BiovaxID and those with IgG isotype tumors who received control vaccine.