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Vaccination with Human Pluripotent Stem Cells Generates a Broad Spectrum of Immunological and Clinical Response against Colon Cancer
Yi Li 1 4, Hui Zeng 2 3 5, Ren-He Xu 2 3, Bei Liu 1 2 *, Zihai Li 1 2 *
1Department of Immunology, University of Connecticut School of Medicine, Farmington, CT 06030-1601
2UConn Stem Cell Institute, University of Connecticut School of Medicine, Farmington, CT 06030-1601
3Department of Genetics and Developmental Biology, University of Connecticut School of Medicine, Farmington, CT 06030-1601
4Department of Gynecology and Obstetrics, Peking University People's Hospital, 100044 Beijing, China
5Department of Hematology, Xiang-Ya Hospital, Central South University, Changsha, Hunan 410008, China
The history of immunizing with embryonic materials to generate an anti-tumor immune response dates back 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, due to lack of uniformed source tissues and ethical challenges. With the availability of well-characterized human pluripotent stem cells, it is now possible to ask if tumor protective immunity could indeed be elicited with stem cells. Herein, we investigated if vaccination with defined human embryonic stem (hES) or induced pluripotent stem (iPS) cells was effective against a colon carcinoma. We discovered that vaccination of mice with hES cell line H9 generated consistent cellular and humoral immune responses against CT26 colon carcinoma. Protection correlated strongly with the expansion of tumor-responsive and interferon -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 hES cell 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 hES cell line in conferring tumor protection, suggesting that there is heterogeneity of expression of oncofetal antigens by hES and iPS cells. We conclude that the hES-based vaccine is a promising modality for immunotherapy of cancer.
