Vaccination with human pluripotent stem cells generates a broad spectrum of immunological and clinical responses against colon cancer.
The history of immunizing with embryonic materials to generate an antitumor immune response dates back to a century ago. The premise is that cancer cells share the expression of oncofetal antigens with embryonic materials and that the immune response against these antigens in the embryonic tissues is cross-protective against cancer. However, such a practice has never advanced beyond experimental animal settings, because of lack of uniformed source tissues and ethical challenges. With the availability of well-characterized human pluripotent stem cells, it is now possible to ask whether tumor protective immunity could indeed be elicited with stem cells. Herein, we investigated whether vaccination with defined human embryonic stem cells (hESCs) or induced pluripotent stem (iPS) cells was effective against a colon carcinoma. We discovered that vaccination of mice with hESC line H9 generated consistent cellular and humoral immune responses against CT26 colon carcinoma. Protection correlated strongly with the expansion of tumor-responsive and interferon-gamma-producing cells and the profound loss of CD11b(+)Gr-1(+) myeloid-derived suppressor cells in the spleen. No evidence of autoimmunity was observed. We also compared the immunogenicity against colon cancer between a hESC line CT2 and an iPS cell line TZ1 that were generated in the same stem cell facility. We found that the iPS cell line was inferior to the hESC line in conferring tumor protection, suggesting that there is heterogeneity of expression of oncofetal antigens by hESCs and iPS cells. We conclude that the hESC-based vaccine is a promising modality for immunotherapy of cancer.
Li
Yi
Y
Department of Immunology, University of Connecticut School of Medicine, Farmington, Connecticut 06030-1601, USA.
Zeng
Hui
H
Xu
Ren-He
RH
Liu
Bei
B
Li
Zihai
Z
D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D000818:Animals; D015551:Autoimmunity; D002454:Cell Differentiation; D002460:Cell Line; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014611:Vaccination; D023041:Xenograft Model Antitumor Assays