Introduction to GRAMS and the Development of LNP Vaccines Using Microfluidic Devices
Koichi Fukase
Osaka University
Executive Vice President
The Group for Research on Automated Flow and Microreactor Synthesis (GRAMS) was established in November 1996 as the Kinka Chemical Society’s "Robotic Synthesis Research Group". Recognizing the importance of flow microreactors early on, the group held Japan's first symposium on microreactors in 1998, inviting speakers from Europe and the United States. In April 2007, it was renamed to GRAMS and has continued its research activities, focusing on the latest trends in the field.
GRAMS holds several member-only study sessions and public symposia annually, where device and equipment companies also conduct demonstrations. Currently, GRAMS collaborates internationally with microflow synthesis groups in countries such as South Korea and Australia to promote research in this field and contribute to the development of the chemical and pharmaceutical industries.
Peptide-based cancer vaccines hold great potential for cancer immunotherapy as they can readily incorporate various antigens. However, due to the low immunogenicity of peptide antigens, self-adjuvanting vaccines—combining antigens and immunostimulatory adjuvants—have gained attention in recent years. The key feature of self-adjuvanting vaccines is the effective induction of antigen-specific immune responses through the co-delivery of antigens and adjuvants to the same immune cells.
In this study, we developed a self-adjuvanting lipid nanoparticle (LNP) vaccine incorporating a peptide antigen into cationic LNPs. This vaccine platform enables the presentation of multivalent antigens and the co-delivery of antigens and adjuvants to the same immune cells. The vaccine contains a breast cancer antigen (CH401 peptide) and adjuvants (Pam3CSK4, α-GalCer, MPLA, and CpG ODN) encapsulated within cationic LNPs. These LNP vaccines were prepared using the microfluidic device, "iLiNP," which enables the formulation of size-controlled LNPs (<100 nm).
The nanoparticulate self-adjuvanting vaccine exhibits favorable physiological properties (<100 nm, spherical shape) that facilitate the efficient co-delivery of antigen and adjuvant to lymph nodes and uptake by dendritic cells. The LNP vaccine efficiently induces CH401-specific antibodies and cellular immunity, demonstrating its potential as a promising tool for cancer immunotherapy.
Keywords: LNP, microfluidic device, vaccine
