An oral cancer vaccine using a Bifidobacterium vector suppresses tumor growth in a syngeneic mouse bladder cancer model

• Published in: Molecular therapy. Oncolytics Vol. 22; pp. 592 - 603
• Main Authors: Kitagawa, Koichi, Tatsumi, Maho, Kato, Mako, Komai, Shota, Doi, Hazuki, Hashii, Yoshiko, Katayama, Takane, Fujisawa, Masato, Shirakawa, Toshiro
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 24.09.2021; American Society of Gene & Cell Therapy; Elsevier
• Subjects: anti-PD-1 antibody; bacterial vector; Bifidobacterium; bladder cancer; cancer vaccine; combination immunotherapy; immune checkpoint inhibitor; oral vaccine; Original; WT1; anti-PD-1 antibody; immune checkpoint inhibitor; Bifidobacterium; cancer vaccine; bacterial vector; WT1; bladder cancer; combination immunotherapy; oral vaccine
• ISSN: 2372-7705; 2372-7705
• DOI: 10.1016/j.omto.2021.08.009

Cancer immunotherapy using immune-checkpoint inhibitors (ICIs) such as PD-1/PD-L1 inhibitors has been well established for various types of cancer. Monotherapy with ICIs, however, can achieve a durable response in only a subset of patients. There is a great unmet need for the ICI-resistant-tumors. Since patients who respond to ICIs should have preexisting antitumor T cell response, combining ICIs with cancer vaccines that forcibly induce an antitumor T cell response is a reasonable strategy. However, the preferred administration sequence of the combination of ICIs and cancer vaccines is unknown. In this study, we demonstrated that combining an oral WT1 cancer vaccine using a Bifidobacterium vector and following anti-PD-1 antibody treatment eliminated tumor growth in a syngeneic mouse model of bladder cancer. This vaccine induced T cell responses specific to multiple WT1 epitopes through the gut immune system. Moreover, in a tumor model poorly responsive to an initial anti-PD-1 antibody, this vaccine alone significantly inhibited the tumor growth, whereas combination with continuous anti-PD-1 antibody could not inhibit the tumor growth. These results suggest that this oral cancer vaccine alone or as an adjunct to anti-PD-1 antibody could provide a novel treatment option for patients with advanced urothelial cancer including bladder cancer. [Display omitted] An oral cancer vaccine using a Bifidobacterium vector completely suppresses mouse bladder tumor growth by combining with anti-PD-1 antibody. Moreover, this vaccine alone significantly inhibits growth of anti-PD-1 antibody-poorly responsive tumor. These results warrant the further clinical development of this oral cancer vaccine.