Design and characterization of the tumor vaccine MGN1601, allogeneic fourfold gene-modified vaccine cells combined with a TLR-9 agonist.
The tumor vaccine MGN1601 was designed and developed for treatment of metastatic renal cell carcinoma (mRCC). MGN1601 consists of a combination of fourfold gene-modified cells with the toll-like receptor 9 agonist dSLIM, a powerful connector of innate and adaptive immunity. Vaccine cells originate from a renal cell carcinoma cell line (grown from renal cell carcinoma tissue), express a variety of known tumor-associated antigens (TAA), and are gene modified to transiently express two co-stimulatory molecules, CD80 and CD154, and two cytokines, GM-CSF and IL-7, aimed to support immune response. Proof of concept of the designed vaccine was shown in mice: The murine homologue of the vaccine efficiently (100%) prevented tumor growth when used as prophylactic vaccine in a syngeneic setting. Use of the vaccine in a therapeutic setting showed complete response in 92% of mice as well as synergistic action and necessity of the components. In addition, specific cellular and humoral immune responses in mice were found when used in an allogeneic setting. Immune response to the vaccine was also shown in mRCC patients treated with MGN1601: Peptide array analysis revealed humoral CD4-based immune response to TAA expressed on vaccine cells, including survivin, cyclin D1, and stromelysin.
Foundation Institute for Molecular Biology and Bioinformatics, Freie Universitaet Berlin, Berlin, Germany; Mologen AG, Berlin, Germany.
Barbara
B
Volz
Mologen AG , Berlin, Germany.
Manuel
M
Schmidt
Foundation Institute for Molecular Biology and Bioinformatics, Freie Universitaet Berlin, Berlin, Germany; Mologen AG, Berlin, Germany.
Kerstin
K
Heinrich
Mologen AG , Berlin, Germany.
Kerstin
K
Kapp
Mologen AG , Berlin, Germany.
Matthias
M
Schroff
Foundation Institute for Molecular Biology and Bioinformatics, Freie Universitaet Berlin , Berlin, Germany.
Burghardt
B
Wittig