Vaccination with IgM but Not IgG Idiotype (proteins) Prolongs Remission Duration In Follicular Lymphoma Patients.
Individuals who responded to initial chemotherapy and remained in remission for at least six months were eligible to continue in the trial, and received either a personalized idiotype vaccine plus an immune-stimulating agent called GM-CSF, or placebo vaccine plus GM-CSF. When researchers analyzed the patients who received at least one dose of personalized vaccine, they saw a 14-month improvement in disease-free survival, compared to those who received the placebo. The 76 patients treated with the vaccine had a median disease-free survival of 44.2 months, compared to 30.6 months for the 41 patients treated with the placebo.
Following a hunch and some earlier observations in the literature, Schuster and co-workers decided to reanalyze the data after dividing the patients based upon the type of isotype protein on their tumor cells’ surface. He found that patients whose tumors had an IgM-idiotype protein had a robust response to the vaccine, with an increase in median disease-free survival from 28.7 months in placebo-treated patients to 52.9 months in vaccine-treated patients. By contrast, the impact of the vaccine on patients whose idiotype protein was part of an IgG-type antibody was negligible, with a non-significant increase from 32.4 months to 35.1 months.
“There is some evidence in the scientific literature that IgG is not as immunogenic or causes immune suppression or tolerance, compared with IgM,” Schuster says, “but no one has tested this hypothesis in a clinical trial.” Although this new analysis was not included in the original trial design, Schuster thinks its importance is clear. “What this analysis is doing is telling us potential ways to make better vaccines,” he says. “And it tells us that we should continue efforts to develop vaccines as part of our treatment for lymphoma.”
In fact, the new analysis may reveal the very reason that previous attempts to make an effective idiotype vaccine have not produced encouraging results. The technology used to develop idiotype vaccines in other trials engineered all the idiotype proteins into an IgG-type. By contrast, this trial used a technique that didn’t restrict idiotype vaccine production to IgG, but rather included whatever protein was native to the patients’ tumors.
To confirm their novel results, Schuster’s team plans to launch a new trial next year using the same vaccine approach, but this time they will divide patients at the outset, according to whether their idiotype protein is an IgM- or IgG-type.
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