Vaccination with Human Pluripotent Stem Cells Generates a Broad Spectrum of Immunological and Clinical Responses Against Colon Cancer

Abstract

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-c-producing cells and the profound loss of CD11b 1 Gr-1 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.

Targeting Stat3 Induces Senescence in Tumor Cells and Elicits Prophylactic and Therapeutic Immune Responses against Breast Cancer Growth Mediated by NK Cells and CD4+ T Cells

“…Different immunization strategies have achieved an immune response that provides tumor cross-protection, such as the administration of colon carcinoma CT26 cells transfected with an IL-12 plasmid, was able to reject the murine breast cancer line LM3 through the participation of CTLs (35), and immunization with irradiated defined human embryonic stem cells was effective at rejecting CT26 cells along with the induction of IFN-g-producing CD4 + T cells (36). However, in vivo NK cell participation in these works was not evaluated.…”

Human Embryonic Stem Cells - a Potential Vaccine for Ovarian Cancer

“…Preliminary data support the role of ESCs as effective cellular agents that reverse the immune dysfunction that is responsible for causing cancer. Moreover, ESCs induce antitumor immunity in tumor loading mice of different types and stages, such as colon and lung carcinoma (Li et al, 2009;Dong et al, 2010;Mocan and Iancu, 2011;Yaddanapudi et al, 2012). It has been a long time since embryonic materials have been used as vaccines to prevent the formation and development of tumors in animal experiments.…”

“…Zu-Juan Zhang, Xin-Hua Chen, Xiao-Hong Chang, Xue Ye, Yi Li*, Heng Cui* would cross-react with cancer cells (Li et al, 2009).…”

“…Li et al (2009) demonstrated the capacity of human ES cells to effectively immunize against murine colon cancer for the first time. This was further supported by three additional studies that embryonic stem cells had successfully provided activation of antitumor immunity, leading to impressive suppression of proliferation and development of malignant colon tumors and lung cancer (Dong et al, 2010;Mocan and Iancu, 2011;Yaddanapudi et al, 2012).…”

Application of Human Pluripotent Stem Cells in T Cell Based Cancer Immunotherapy

“…Interestingly, a recent study in mouse model has demonstrated anti-tumor effect of hES cells [62], in support of the long standing view that the administration of embryonic materials can induce antitumor effect [63]. Although these findings are encouraging, the prevailing ethical and moral issues associated with the derivation of HLA matched embryonic material and the tumorigenic potential of the hPS cells makes the therapeutic application of hPS cells as anti-cancer immunogenic agents a challenge.…”