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

• DOI: 10.1016/j.omto.2021.08.009
• Publication Date: 2021-08-25T04:04:07Z
• Authors: Koichi Kitagawa; Maho Tatsumi; Mako Kato; Shota Komai; Hazuki Doi; Yoshiko Hashii; Takane Katayama; Masato Fujisawa; Toshiro Shirakawa
• Keywords: anti-PD-1 antibody; 0303 health sciences; 03 medical and health sciences; bladder cancer; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Original Article; Bifidobacterium; bacterial vector; cancer vaccine; oral vaccine; RC254-282; 3. Good health

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.