Vaccination with embryonic stem cells protects against lung cancer: is a broad-spectrum prophylactic vaccine against cancer possible?

• Published in: PloS one 2012-07, Vol.7 (7), p.e42289
• Main Authors: Yaddanapudi, Kavitha, Mitchell, Robert A, Putty, Kalyani, Willer, Sharon, Sharma, Rajesh K, Yan, Jun, Bodduluri, Haribabu, Eaton, John W
• Format: Article
• Language: English
• Subjects: Animals; Antigen (tumor-associated); Antigens; Biology; Cancer; Cancer genetics; Cancer vaccines; Cancer Vaccines - administration & dosage; Carcinogens; Carcinoma, Lewis Lung - immunology; Carcinoma, Lewis Lung - prevention & control; CD25 antigen; CD4 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Colony-stimulating factor; Cytokines - biosynthesis; Cytotoxicity; Dendritic cells; Embryo cells; Embryo fibroblasts; Embryonic Stem Cells; Embryos; Fibroblasts; Foxp3 protein; Gene expression; Genetic aspects; Granulocyte-macrophage colony-stimulating factor; House mouse; Immunity; Immunologic Memory; Immunological memory; Immunostimulation; Immunotherapy; Leukocytes (granulocytic); Lung cancer; Lung carcinoma; Lung diseases; Lymphocytes; Lymphocytes T; Macrophages; Medical prognosis; Medicine; Melanoma; Mice; Ovarian cancer; Similarity; Spleen; Stem cell transplantation; Stem cells; Studies; Suppressor cells; Surgical implants; T cells; Tumorigenesis; Tumors; Vaccination; Vaccine efficacy; Vaccines
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0042289

The antigenic similarity between tumors and embryos has been appreciated for many years and reflects the expression of embryonic gene products by cancer cells and/or cancer-initiating stem cells. Taking advantage of this similarity, we have tested a prophylactic lung cancer vaccine composed of allogeneic murine embryonic stem cells (ESC). Naïve C57BL/6 mice were vaccinated with ESC along with a source of granulocyte macrophage-colony stimulating factor (GM-CSF) in order to provide immunostimulatory adjuvant activity. Vaccinated mice were protected against subsequent challenge with implantable Lewis lung carcinoma (LLC). ESC-induced anti-tumor immunity was not due to a non-specific "allo-response" as vaccination with allogeneic murine embryonic fibroblasts did not protect against tumor outgrowth. Vaccine efficacy was associated with robust tumor-reactive primary and memory CD8(+) T effector responses, Th1 cytokine response, higher intratumoral CD8(+) T effector/CD4(+)CD25(+)Foxp3(+) T regulatory cell ratio, and reduced myeloid derived suppressor cells in the spleen. Prevention of tumorigenesis was found to require a CD8-mediated cytotoxic T lymphocyte (CTL) response because in vivo depletion of CD8(+) T lymphocytes completely abrogated the protective effect of vaccination. Importantly, this vaccination strategy also suppressed the development of lung cancer induced by the combination of carcinogen administration and chronic pulmonary inflammation. Further refinement of this novel vaccine strategy and identification of shared ESC/tumor antigens may lead to immunotherapeutic options for lung cancer patients and, perhaps more importantly, could represent a first step toward the development of prophylactic cancer vaccines.