MP06-12 A WT1 ORAL CANCER VACCINE USING A BIFIDOBACTRERIUM VECTOR SUPPRESSES GROWTH OF ANTI-PD-1 ANTIBODY-RESISTANT MOUSE BLADDER TUMOR

Abstract

You have accessJournal of UrologyCME1 May 2022MP06-12 A WT1 ORAL CANCER VACCINE USING A BIFIDOBACTRERIUM VECTOR SUPPRESSES GROWTH OF ANTI-PD-1 ANTIBODY-RESISTANT MOUSE BLADDER TUMOR Toshiro Shirakawa, Koichi Kitagawa, Hideto Ueki, Junya Furukawa, Nobuyuki Hinata, and Masato Fujisawa Toshiro ShirakawaToshiro Shirakawa More articles by this author , Koichi KitagawaKoichi Kitagawa More articles by this author , Hideto UekiHideto Ueki More articles by this author , Junya FurukawaJunya Furukawa More articles by this author , Nobuyuki HinataNobuyuki Hinata More articles by this author , and Masato FujisawaMasato Fujisawa More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002523.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cancer immunotherapy with immune-checkpoint inhibitors (ICIs) including PD-1/PD-L1 inhibitors has been well established for various types of cancer including bladder cancer. Monotherapy with ICIs, however, can achieve a durable response in only a subset of patients. There is a great unmet need for ICI-resistant tumors. Although combining ICIs with cancer vaccines which forcibly induce an antitumor T cell response is a reasonable strategy, the preferred administration sequence is unknow. In our previous study, we demonstrated that an oral cancer vaccine, a recombinant Bifidobactrerium (B.) longum displaying a WT1 tumor associated antigen, inhibited the tumor growth in a TRAMP-C2 mouse prostate cancer tumor model and that its anti-tumor activity could be augmented by an anti-PD-1 antibody (Molecular Cancer Therapeutics, 2019;18:980-). In the present study we explored the feasibility of this oral vaccine in a mouse syngeneic bladder cancer model. METHODS: A recombinant B. longum 420 strain that expresses partial murine-WT1 protein fused to galacto-N-biose/lacto-N-biose I binding protein, which we used as an anchor to display antigen on the bacterial cell surface, was constructed. MBT-2, which is a bladder cancer cell line originated from C3H/He mice and endogenously expresses WT1 protein, was used to generate a syngeneic subcutaneous tumor model. Mice were orally administered 1.0×109 colony-forming units of B. longum 420, 5 times a week for 5 weeks, using a feeding needle. For an anti-PD-1 antibody treatment, 200μg of anti-PD-1 antibody was intraperitoneally injected into mice twice a week for 2 weeks. Tumors continuously grew despite the initial anti-PD-1 treatment were selected as the anti-PD-1 antibody-resistant tumor. In addition, immunological responses including tumor-infiltrating lymphocytes (TILs) were thoroughly analyzed. RESULTS: Combining B. longum 420 and following anti-PD-1 antibody treatment completely suppressed the MBT-2 tumor growth and cured all mice tested, while all anti-PD-1 antibody treated mice died. The significantly increased CD4 and CD8 positive T cells were observed in the TILs of combination treatment group. Moreover, in the anti-PD-1 antibody-resistant tumor model, this vaccine alone significantly inhibited the tumor growth, while combination with continuous anti-PD-1 antibody could not inhibit the tumor growth. Interestingly, the number of regulatory T cells in TILs of the vaccine alone group was significantly smaller than the combination treatment group. CONCLUSIONS: 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 bladder cancer. Source of Funding: Japan Agency for Medical Research and Development (AMED): 20lm0203091h0002 © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e81 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Toshiro Shirakawa More articles by this author Koichi Kitagawa More articles by this author Hideto Ueki More articles by this author Junya Furukawa More articles by this author Nobuyuki Hinata More articles by this author Masato Fujisawa More articles by this author Expand All Advertisement PDF DownloadLoading ...