Abstract
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.
Highlights
The cancer-preventive effects of probiotics, for example, Lactobacillus against colorectal cancer, have long been reported.[1]
B. longum 420 induced tumor-specific cellular immunity through the gut immune system To determine whether oral administration of B. longum 420 could induce MBT-2 cell-specific cellular immunity through the gut immune system, we orally administrated B. longum 420 to C3H/ He mice and isolated splenocytes or lymphocytes from spleen, mesenteric lymph nodes (MLNs), and Peyer’s patch (PP) to perform immunological assays
These results indicated that B. longum 420 can activate the splenocytes along with IFN-g secretion, which plays an important role in Th1 immune responses,[31] by stimulation with MBT-2 cells
Summary
The cancer-preventive effects of probiotics, for example, Lactobacillus against colorectal cancer, have long been reported.[1]. 592 Molecular Therapy: Oncolytics Vol 22 September 2021 a 2021 The Author(s). Www.moleculartherapy.org vaccine,[18] and a recombinant B. longum displaying Wilms’ tumor 1 (WT1) protein as a cancer vaccine.[19] The WT1 gene encodes a zinc finger transcription factor, plays an important role for the normal development of urogenital organs, and is overexpressed in various tumors, such as leukemia, colon cancer, breast cancer, prostate cancer, urothelial cancer, and pediatric kidney tumors (Wilms’ tumor).[20,21] In addition, WT1 was ranked as the No 1 antigen among 75 tumor antigens by the National Cancer Institute pilot project developing a priority list of tumor vaccine target tumor-associated antigens.[22]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
