BAMLET, a bovine α-lactalbumin - oleic acid complex, is a novel and promising candidate for the treatment of cancer because of its capacity to specifically kill tumor cells while leaving normal cells and tissues relatively unharmed. While recent studies focused on direct tumoricidal effects of BAMLET, we investigated the potential of BAMLET to modulate anti-tumor immune responses, in combination with the TLR7 agonist R848, which stimulates innate and adaptive immunity.
Consistent with previous studies, BAMLET induced killing of B16 melanoma cells in vitro. Interestingly, we demonstrated for the first time that BAMLET also has immunostimulatory effects. BAMLET enhanced R848-induced dendritic cell (DC) maturation and IL-12, TNF and IL-6 production, which are crucial for the induction of adaptive immune responses against tumors. Moreover, DCs stimulated with BAMLET and R848 were capable of activating CD4 T cells in vitro. Treatment of tumor bearing mice with either BAMLET or R848 alone conferred some protection against tumor growth. However, treatment with a combination of BAMLET and R848 conferred a high level of protection, with 57% of mice completely rejecting the tumor. We found a higher frequency of DCs and IFNγ-secreting T cells in the tumor draining lymph nodes and spleens of mice treated with the combination of BAMLET and R848, compared with untreated mice or mice treated with either BAMLET or R848 alone.
Our data are consistent with a role for BAMLET in directly killing tumor cells, which release antigens that are taken up by DCs, but suggest that BAMLET can also promote maturation and secretion of T cell polarizing cytokines by DCs, especially when co-activated through a TLR. These activated DCs promote induction of IFNγ-secreting CD4 T cells that have anti-tumor activity. In conclusion, we demonstrated that BAMLET and R848 are a promising combination therapy against cancer as they target tumor cells directly, but also activate anti-tumor immune responses.
Citation Format: Lydia Dyck, Níal Harte, Kenneth Hun Mok, Kingston H.G. Mills. BAMLET in combination with the TLR7 agonist R848 protects against melanoma in a murine model. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B68.
- ©2015 American Association for Cancer Research.