Evidence of Antitumor and Antimetastatic Potential of Induced Pluripotent Stem Cell-Based Vaccines in Cancer Immunotherapy

Masae Kishi; Afag Asgarova; Christophe Desterke; Diana Chaker; Jérôme Artus; Ali G Turhan; Annelise Bennaceur-Griscelli; Frank Griscelli

doi:10.3389/fmed.2021.729018

Evidence of Antitumor and Antimetastatic Potential of Induced Pluripotent Stem Cell-Based Vaccines in Cancer Immunotherapy

Front Med (Lausanne). 2021 Dec 10:8:729018. doi: 10.3389/fmed.2021.729018. eCollection 2021.

Authors

Masae Kishi¹, Afag Asgarova¹, Christophe Desterke^{1

2}, Diana Chaker¹, Jérôme Artus^{1

2}, Ali G Turhan^{1

2

3}, Annelise Bennaceur-Griscelli^{1

2

3}, Frank Griscelli^{1

4

5}

Affiliations

¹ Institut National de la Santé et de la Recherche Médicale (INSERM) UA9-Human Pluripotent Stem Cell Core Facility, CITHERA Infrastructure-INGESTEM, Villejuif, France.
² Université Paris-Saclay, Faculté de Médecine, Kremlin Bicêtre, France.
³ APHP Paris-Saclay Service d'Hématologie, Hôpital Universitaire Paris Sud (AP-HP), Kremlin Bicêtre, France.
⁴ Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
⁵ Département de Biologie Médicale et Pathologie Médicales, Gustave Roussy Cancer Campus, Villejuif, France.

Abstract

Cancer is maintained by the activity of a rare population of self-renewing "cancer stem cells" (CSCs), which are resistant to conventional therapies. CSCs over-express several proteins shared with induced pluripotent stem cells (iPSCs). We show here that allogenic or autologous murine iPSCs, combined with a histone deacetylase inhibitor (HDACi), are able to elicit major anti-tumor responses in a highly aggressive triple-negative breast cancer, as a relevant cancer stemness model. This immunotherapy strategy was effective in preventing tumor establishment and efficiently targeted CSCs by inducing extensive modifications of the tumor microenvironment. The anti-tumoral effect was correlated with the generation of CD4+, CD8+ T cells, and CD44+ CD62L- CCR7low CD127low T-effector memory cells, and the reduction of CD4+ CD25+FoxP3+ Tregs, Arg1⁺ CD11b+ Gr1+, and Arg1⁺ and CD11b+ Ly6+ myeloid-derived suppressor cell populations within the tumor. The anti-tumoral effect was associated with a reduction in metastatic dissemination and an improvement in the survival rate. These results demonstrate for the first time the clinical relevance of using an off-the-shelf allogeneic iPSC-based vaccine combined with an HDACi as a novel pan-cancer anti-cancer immunotherapy strategy against aggressive tumors harboring stemness features with high metastatic potential.

Keywords: CSC; HDACi; breast cancer; iPSCs; vaccine.