Autologous iPSC-Based Vaccines Elicit Anti-tumor Responses In Vivo

Kooreman, Nigel G.; Kim, Young-Kyun; Almeida, Patrícia E. de; Termglinchan, Vittavat; Diecke, Sebastian; Shao, Ning‐Yi; Wei, Tzu-Tang; Yi, Hyoju; Dey, Devaveena; Nelakanti, Raman; Brouwer, Thomas P.; Paik, David T.; Sagiv-Barfi, Idit; Han, Arnold; Quax, Paul H.A.; Hamming, Jaap F.; Levy, Ronald; Davis, Mark M.; Wu, Joseph C.

doi:10.1016/j.stem.2018.01.016

Cited by 123 publications

(111 citation statements)

References 54 publications

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“…Very recently, Kooreman et al [28] demonstrated that murine autologous fibroblast-derived miPSC-based vaccines generated anticancer immunity against various types of cancers, including melanoma, breast cancer and mesothelioma. They based their studies on the thesis that iPSCs and cancer cells share a broad spectrum of epitopes.…”

Section: Discussionmentioning

confidence: 99%

Novel Genetic Melanoma Vaccines Based on Induced Pluripotent Stem Cells or Melanosphere-Derived Stem-Like Cells Display High Efficacy in a murine Tumor Rejection Model

Gąbka-Buszek

Kwiatkowska-Borowczyk

Jankowski

et al. 2020

Vaccines

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Therapeutic cancer vaccines have elicited renewed interest due to the development of immune checkpoint inhibitors. The role of these vaccines is to induce specific effector cells for killing cancer cells. Cancer stem cells (CSCs) are responsible for tumor growth and progression. Accordingly, they are targets for various cancer therapies, including immunotherapy. Here, we demonstrate the effectiveness of melanoma vaccines composed of genetically modified tumor cells admixed with melanoma stem-like cells (MSC) or induced pluripotent stem cells (iPSCs). Two vaccines were constructed. The first vaccine contained cells derived from B16F10 melanospheres (SFs) with CSC characteristics. The second vaccine contained syngeneic murine induced pluripotent stem cells (miPSCs). iPSCs or SF cells were admixed with B16F10 cells, modified with the designer cytokine Hyper-IL6(H6) (B16/H6). Control mice received B16/H6 cells, B16F10 cells or PBS. Immunization with either vaccine significantly inhibited tumor growth and increased disease-free survival (DFS) and overall survival (OS) in C57BL/6 mice. Mice treated with the SF or iPSC vaccine demonstrated increased activation of the immune response in the vaccination site and tumor microenvironment compared to those treated with B16/H6, B16F10 or PBS. Higher infiltration of dendritic cells (DCs) monocytes, and natural killer (NK) cells; lower numbers of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs); higher levels of the cytokines INFγ and IL-12 were observed with the novel vaccines than with the control treatments. In vitro restimulation of splenocytes derived from mice immunized with B16F10 cell, SF cell or miPSC lysates increased the proliferation of CD4+ T helper lymphocytes and secretion of cytokines. An increased serum titer of antibodies directed against B16F10 cells was found in mice immunized with the SF vaccine. The most effective DFS and OS extensions were reached with the miPSCs vaccine. The described results form the basis for a novel platform for the next generation of cancer vaccines composed of allogeneic cancer-specific cells modified with a molecular adjuvant gene and admixed with allogeneic miPSCs or SFs.

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Section: Discussionmentioning

confidence: 99%

Novel Genetic Melanoma Vaccines Based on Induced Pluripotent Stem Cells or Melanosphere-Derived Stem-Like Cells Display High Efficacy in a murine Tumor Rejection Model

Gąbka-Buszek

Kwiatkowska-Borowczyk

Jankowski

et al. 2020

Vaccines

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“…Therefore, it is possible to induce immune responses toward normal tissues. Nigel et al did not observe autoimmunity after treatment with autologous iPSC vaccine [11]; however, further investigation needs to be carried out to confirm the safety of the approach.…”

Section: Increased Immune Responses and Autoimmunitymentioning

confidence: 97%

“…These iPSCs share the same characteristics with ESCs while removing ethical concerns from embryo destruction. Till now, both hESCs and iPSCs are important sources for the induction of effector T-and NK cells [7][8][9][10], and for the production of anti-cancer vaccines [11,12], which will be discussed later in this review.…”

Section: Pluripotent Stem Cells (Pscs)mentioning

confidence: 99%

“…Meanwhile, vaccines produced by ESCs/iPSCs-derived multiple antigens would offer more applications to treat cancers. Main concerns are the possibility of tetratoma formation and induction of autoimmunity [11,104,105]. In comparison to a xenogeneic source, allogeneic ESCs and autologous iPSCs-based vaccines were found more effective to prevent tumor relapse in mice, as evidenced by enhanced immune cell proliferation and cytotoxic cytokine production [104][105][106][107].…”

Section: Stem Cell-based Anti-cancer Vaccinesmentioning

confidence: 99%

“…Preformed tumors with a strong immunosuppressive microenvironment could reduce the efficacy of vaccine treatment [108]. To enhance anti-tumor immunity, combination with other therapies, such as surgery, radiation therapy, chemotherapy, immune checkpoint inhibitors, and adjuvants, is necessary [11].…”

Section: Stem Cell-based Anti-cancer Vaccinesmentioning

confidence: 99%

See 2 more Smart Citations

Recent Progress of Stem Cell Therapy in Cancer Treatment: Molecular Mechanisms and Potential Applications

Chu

Nguyen

Tien

et al. 2020

Cells

125

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The insufficient and unspecific target of traditional therapeutic approaches in cancer treatment often leads to therapy resistance and cancer recurrence. Over the past decades, accumulating discoveries about stem cell biology have provided new potential approaches to cure cancer patients. Stem cells possess unique biological actions, including self-renewal, directional migration, differentiation, and modulatory effects on other cells, which can be utilized as regenerative medicine, therapeutic carriers, drug targeting, and generation of immune cells. In this review, we emphasize the mechanisms underlying the use of various types of stem cells in cancer treatment. In addition, we summarize recent progress in the clinical applications of stem cells, as well as common risks of this therapy. We finally give general directions for future studies, aiming to improve overall outcomes in the fight against cancer.

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

Jin

Tong

et al. 2022

Adv Healthcare Materials

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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.

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Autologous iPSC-Based Vaccines Elicit Anti-tumor Responses In Vivo

Cited by 123 publications

References 54 publications

Novel Genetic Melanoma Vaccines Based on Induced Pluripotent Stem Cells or Melanosphere-Derived Stem-Like Cells Display High Efficacy in a murine Tumor Rejection Model

Novel Genetic Melanoma Vaccines Based on Induced Pluripotent Stem Cells or Melanosphere-Derived Stem-Like Cells Display High Efficacy in a murine Tumor Rejection Model

Recent Progress of Stem Cell Therapy in Cancer Treatment: Molecular Mechanisms and Potential Applications

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

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