A novel intradermal idiotype vaccine elicited specific immune responses in patients with advanced B-cell lymphoma despite profound immunosuppression

08-21-2006

A novel intradermal idiotype vaccine elicited specific immune responses in patients with advanced B-cell lymphoma despite profound immunosuppression.

Researchers in Germany noted, "The immunoglobulin receptor of B-cell lymphomas constitutes a specific tumor antigen (idiotype) and a target for active immunotherapy. Encouraging results have been reported in phase II trials after s.c. vaccination of follicular lymphoma patients during clinical remission with idiotype produced from eukaryotic cell lines and coupled to an immunogenic carrier macromolecule."

"We have developed a good manufacturing protocol for rapid expression of idiotype vaccines as recombinant Fab fragments in Escherichia coli," said Cristina Bertinetti and colleagues at Freiburg University. "The objectives of this trial were to show safety and feasibility of intradermal immunization with this vaccine and to investigate whether immune responses were induced by this immunization route."

"Patients (n=18) with advanced B-cell malignancies received repetitive intradermal vaccinations with 0.5 to 1.65 mg recombinant idiotype Fab fragment mixed with lipid-based adjuvant in combination with 150 mcg granulocyte macrophage colony-stimulating factor s.c. at the same location," they explained. "The patients' immune status was assessed by flow cytometry of peripheral blood lymphocytes and concomitant hepatitis B vaccination. Cellular and humoral immune responses to the vaccine were assessed by enzyme-linked immunospot and ELISA."

"Side effects of a total of 65 vaccinations were mild and did not affect the immunization schedule," the researchers reported. "No patient developed hepatitis B surface antibodies (anti-HBs) after two hepatitis B immunizations. Of 17 evaluable patients, five developed specific anti-vaccine antibodies and eight developed anti-Fab T-cell responses. T-cell reactivity was independent of the cellular immune status and was idiotype specific as shown by statistical regression analysis (p=0.0024) and epitope mapping studies."

The researchers concluded, "Intradermal administration of uncoupled recombinant idiotype with appropriate adjuvants may overcome profound clinical immunosuppression and induce specific immune responses."

Bertinetti and associates published their study in Cancer Research (Phase I trial of a novel intradermal idiotype vaccine in patients with advanced B-cell lymphoma: Specific immune responses despite profound immunosuppression. Cancer Res, 2006;66(8):4496-4502).

For additional information, contact Hendrik Veelken, Department of Hematology/Oncology, Freiburg University Medical Center, Hugstetter Strasse 55, D-79106 Freiburg, Germany. hendrik.veelken@uniklinik-freiburg.de.

This article was prepared by Clinical Trials Week editors from staff and other reports. Copyright 2006, Clinical Trials Week via NewsRx.com.