The Epitope Basis of Embryonic Stem Cell‐Induced Antitumor Immunity against Bladder Cancer

Abstract

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) share many cellular and molecular features with cancer cells. Taking advantage of these similarities, stem cells are effective vaccines against cancers in animal models. However, the molecular basis is not well understood, which hinders the development of effective cancer vaccines. Here, prophylactic and therapeutic bladder cancer vaccines composed of allogeneic ESCs and CpG with or without granulocyte macrophage colony stimulating factor are tested. The ESC‐based cancer vaccines are able to induce specific antitumor immunity including stimulating cytotoxic CD8+ T cells and memory CD4+ T cells, reducing myeloid‐derived suppressor cells, and preventing bladder cancer growth in mouse models. Furthermore, several genes that are overexpressed in both ESCs and tumors are identified. An epitope‐based vaccine designed with shared overexpressed proteins induces specific antitumor immunity and reduces bladder cancer growth. Functional epitopes underlying the action of stem cell‐based vaccines against bladder cancer are identified and it is confirmed that ESC‐based anticancer vaccines have great potential. A systematic approach is provided here to developing novel effective epitope‐based cancer vaccines in the future.

Enhancing immune responses of ESC-based TAA cancer vaccines with a novel OMV delivery system

“…We showed that OMV-P significantly decreased tumor size in both the bladder cancer and lung cancer models. In agreement with the results from our previous research [ 1 ], the flow cytometry analysis revealed elevated ratios of CD8 + effector T cells, CD4 + memory T cells, and CD8. + memory T cells in OMV-P-treated mice, which suggests ESC-based epitopes have the potential to inhibit different types of tumor growth via inducing antitumor T cell responses.…”

“…Currently, a wide range of vaccines based on ESCs-derived oncofetal antigens are being tested in pre-clinical studies for their potential in inhibiting tumor growth [ 32 – 34 ], while some single-epitope vaccines have already reached stage I/II clinical trials [ 35 ]. In our previous study, we reported that TAAs shared by both ESCs and tumor cells could potently trigger an immune response against bladder cancer [ 1 ]. However, peptide-based vaccines have issues of short half-life of peptides and short-lived antitumor immune response in vivo [ 36 ].…”

“…Immunotherapies have been gaining increasing attention and taking the spotlight away from conventional treatment methods [ 1 , 2 ]. Cancer vaccines have the potential to target a broader set of intracellular antigens and to prime tumor-reactive T cells [ 3 ].…”

“…Moreover, ESCs or iPSCs can express tumor-associated antigens (TAAs) that contain MHC class I or MHC class II epitopes, which could potentially be developed into cancer vaccines. In our previous study, several of these expressed TAAs were identified to have great immunotherapy potential against bladder cancer [ 1 ]. Here, we further evaluated the therapeutic effects of these antigens as a universal tumor vaccine.…”