Infection-mimicking poly(γ-glutamic acid) as adjuvant material for effective anti-tumor immune response

Bio-derived low molecular weight poly(gamma-glutamic acid) (gamma-PGA) was suggested as a novel adjuvant material for use in cancer vaccines. When the infection-mimicking gamma-PGA was immunized with ovalbumin (OVA) as a model antigen, increase in the dendritic cell (DC)-mediated functions such as activation, maturation, antigen uptake, migration to lymph nodes, and priming of lymphocytes, which included cross-presentation, was observed. These DC-mediated functions were found to be facilitated by gamma-PGA in a dose-dependent manner, with stimulation of toll-like receptor 4 (TLR4) being one of the underlying mechanisms. The in vivo efficacy of gamma-PGA was tested in a mouse tumor model where both arms of adaptive immunity (humoral and cell-mediated) were found to be significantly enhanced in the presence of gamma-PGA, indicating efficient priming of B and T cells. Moreover, immunization of mice with gamma-PGA followed by EG7-OVA tumor challenge led to dramatic inhibition of tumor growth. After 71 days, the cured mice were rechallenged with tumor cells at a distant site in order to test the memory effect. No tumor growth was observed, which indicates the presence of a systemic, long-lasting immune response. Based on these results, low molecular weight gamma-PGA is expected to have tremendous potential for applications in cancer immunotherapy. (C) 2015 Elsevier B.V. All rights reserved.