Abstract 2590: Oral combined therapy with probiotics and alloantigen induces B cell dependent long lasting specific tolerance

Background. Allogeneic hematopietic stem cell transplantation (aHSCT) is widely used for the treatment of hematologic malignancies. Although aHSCT provides a good response against the malignant cells (GVL), it also leads to the development of graft-versus-host disease (GVHD), a severe disease with high mortality and morbidity rates. Therapy for GVHD is commonly based on non-specific immunosupression of the transplanted recipient, resulting in the concomitant inhibition of the GVL effect. Material and Methods. Here we propose an alternative approach to specifically suppress GVHD, while sparing the GVL, based on oral treatment of transplant donors with recipient antigens, associated with the intake of probiotic Lactococcus lactis as tolerogenic adjuvant (combined therapy). Results. We show that treatment of C57Bl/6 donor mice with combined therapy before the transplant protects the recipients F1 (C57Bl/6XBAL/c) mice from clinical and pathological manifestations of disease, resulting in 100% survival rate. Importantly, the animals keep the immunological competence maintaining the GVL response as well as the response to third party antigens. The protection is specific, long lasting and dependent on donor IL-10 sufficient B cells activity which induces regulatory T cells in the host. Conclusion. These data suggest that combined therapy is a promising strategy for prevention of GVHD with preservation of GVL, opening new possibilities to treat human patients subjected transplantation. Note: This abstract was not presented at the meeting. Citation Format: Ana Carolina T. Mercadante, Suelen Perobelli, Ana Paula G. Alves, Triciana Goncalves-Silva, Wallace Mello, Ana C Gomes-Santos, Anderson Miyoshi, Ana Maria C. Faria, Adriana Bonomo. Oral combined therapy with probiotics and alloantigen induces B cell dependent long lasting specific tolerance. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2590. doi:10.1158/1538-7445.AM2014-2590