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Development of optimised recombinant idiotypic vaccines for subset-specific immunotherapy of B cell lymphomas

Obiettivo

Therapeutic vaccines targeting B cell non-Hodgkin lymphoma (NHL) idiotype (Id) represent a promising immunotherapeutic approach for a more effective control of these malignancies. A broad use of Id-based vaccination, however, is hampered by the complexity and costs due to the individualized production of these vaccines. Recent evidence suggests that these limitations may be overcome. In fact, distinct sets of stereotyped immunoglobulins have been identified in various B-NHL, suggesting that a much higher frequency of shared Id exists among patients than appreciated previously. We found that the VK3-20 protein, frequently expressed by HCV-related B-NHL, induces specific T cell responses that cross-react against related VK proteins commonly used by different B cell lymphoproliferations. These findings provide the rationale to develop recombinant vaccines using Id shared by different B cell malignancies. Through the complementary and synergistic work of academic partners and three SMEs, we plan to develop and produce optimized recombinant Id vaccines for subset-specific immunotherapy. A database of VH and VL sequences expressed by low-grade B-NHL and chronic lymphocytic leukemias will be established and analyzed to identify subgroups of tumours expressing molecularly correlated Id proteins. Selected Id proteins will be characterized for their immunogenicity and, particularly, for the ability to induce 'cross-reactive¿ immune responses against related Id proteins. B and T cell epitopes will be identified using innovative approaches (pentamer libraries, MATRIX-SCAN) and dedicated assays for immunomonitoring will be developed. Moreover, optimized versions of selected Id vaccines will be produced using new strategies (Gly-Ala repeat insertion, peptide sequence optimization) and validated in animal models. New adjuvants and delivery systems for improved Id vaccine formulations and administration will be also evaluated and validated. The most promising Id proteins will be...

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FP6-2005-LIFESCIHEALTH-7
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CENTRO DI RIFERIMENTO ONCOLOGICO
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Indirizzo
Via Franco Gallini 2
AVIANO PN
Italia

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