Abstract LB-116: Strong MAGE-A3-specific humoral and cellular immune responses in multiple myeloma patients receiving MAGE-A3 protein immunotherapy and peripheral blood lymphocyte reconstitution

MAGE-A3 is an immunogenic tumor-associated antigen expressed in multiple myeloma (MM) patients and conferring poor prognosis, making it a rational target for immunotherapy. Recombinant MAGE-A3 protein was administered in AS15 immunostimulant (containing MPL, QS-21, and CpG 7909) to 13 MM patients pre- and post-autologous stem cell transplant (ASCT) coupled with infusion of vaccine-primed autologous peripheral blood lymphocytes (PBL) early post-ASCT (NCT01380145). All patients had MAGE-A+ myeloma cells at baseline and had an acceptable safety profile during immunotherapy.Robust antibody responses against MAGE-A3 (assessed by ELISA) were induced in all 13 subjects, with high antibody titers (1:10^4-10^6) that persisted to at least 1-year post-ASCT. Subclass analysis demonstrated a prevalence of IgG1 and IgG3. Epitope mapping identified 7 distinct epitopes clustering in hydrophilic regions of MAGE-A3.Peripheral blood T cell responses were evaluated in 8 subjects by IFNγ-ELISpot after in vitro re-stimulation with MAGE-A3 overlapping peptide pools. All patients quickly developed strong MAGE-A3-specific CD4 responses post-vaccination and ASCT, persisting 1-year post-ASCT. Intracellular cytokine staining confirmed polyfunctional, Th1-biased CD4 T cell responses. One patient developed CD8 responses against MAGE-A3 that recognized naturally processed antigen.To date, 6 patients relapsed and 1 died of progressive MM, with no notable difference in cytogenetics or antibody titers compar...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Clinical Research (Excluding Clinical Trials) Source Type: research