Humoral Immune Responses against the Immature Laminin Receptor Show Prognostic Significance in Patients with Multiple Myeloma.

Multiple myeloma (MM) is characterized by a highly variable clinical course. The role of an autologous tumor-specific immune control contributing to the variable length of survival in MM is poorly understood. In the current study, we investigated whether humoral immunity specific for the tumor-associated oncofetal antigen/immature laminin receptor (OFA/iLR) has a prognostic value in MM. In patients with monoclonal gammopathy of unknown significance (MGUS) we found significant levels of anti-OFA/iLR antibodies in 21 of 30 sera (70%) and in 7 of 27 (26%) patients with asymptomatic MM (AMM). In contrast, in sera from patients with progressive MM (n=67) and in normal healthy donors (HD, n=60) no humoral reactivity against OFA/iLR was present. To look on long-term persistence of humoral anti-OFA/iLR immune responses, significant and stable titers of anti-OFA/iLR-specific IgG antibodies in follow-up samples of MGUS patients were detected. IgG subclass analyses showed a predominant IgG1 and IgG3 response suggestive for a Th1-driven immune response in the vast majority of patients with MGUS and to smaller extent in patients with AMM. OFA/iLR-antibodies were capable of recognizing and selectively killing OFA/iLR-expressing myeloma cells in complement-mediated and antibody-dependent cellular cytotoxicity (ADCC) assays. To determine whether the presence of anti-OFA/iLR antibodies influenced progression-free survival (PFS), patients were analyzed according to the presence/absence of a humoral immune response against OFA/iLR protein. In a univariate analysis, the group of patients with reactive sera (n=28) showed a significantly lower probability of disease progression compared to patients with non-reactive sera (n=29). In the patient group with significant anti-OFA/iLR titers only 2 of 28 patients developed disease progression, but 18 of 29 patients with OFA/iLR non-reactive sera (p=0.001). Our data suggest that spontaneous tumor-specific humoral immune responses against OFA/iLR exist in a significant proportion of MM patients and that superior PFS in those patients could reflect autologous immune control.