Physiologic Oxygen Levels Induce a Novel Adjuvant, "Annexin II": Implications for Brain Tumor Vaccines
Neuro-oncology Fellowship, Massachusetts General Hospital
Neurology Resident Physician, NewYork-Presbyterian Hospital/Weill-Cornell Medical Center
Undergraduate Institution and Major/Degree:
B.A. Chemistry, May 2005, St. Olaf College, Northfield, MN
- Walter Low, Ph.D.
- Michael Olin
Weill Cornell Medical Center, Neurology Residency, New York
Malignant gliomas are aggressive neoplasms that respond poorly to surgery, radiation, and chemotherapy. Glioblastoma multiforme (WHO grade IV) kills roughly 70% of patients within two years of diagnosis. Immunotherapy holds great promise as a cell-specific, non-invasive approach, as shown in many phase I clinical trials.
We have increased the effectiveness of our vaccines derived from tumor cultures by placing them in a physiologic oxygen environment. This decrease in oxygen (from atmospheric O2, 20.95% to 5%) enriches the expression of annexin A2 in gliomas. Annexin A2 has immune adjuvant activity, and my thesis project involves understanding annexin A2's activation of dendritic cells, which initiate anti-glioma CD8 T cell responses.
- Andersen BM, Xia J, Epstein AL, Ohlfest JR, Chen W, Blazar BR, Pennell CA, Olin MR. Monomeric annexin A2 is an oxygen-regulated toll-like receptor 2 ligand and adjuvant. J Immunother Cancer. 2016 Feb 16;4:11.
- Olin MR, Pluhar GE, Andersen BM, Shaver R, Waldron NN, Moertel CL. Victory and defeat in the induction of a therapeutic response through vaccine therapy for human and canine brain tumors: a review of the state of the art. Crit Rev Immunol. 2014;34(5):399-432.
- Moertel CL, Xia J, LaRue R, Waldron NN, Andersen BM, Prins RM, Okada H, Donson AM, Foreman NK, Hunt MA, Pennell CA, Olin MR. CD200 in CNS tumor-induced immunosuppression: the role for CD200 pathway blockade in targeted immunotherapy. J Immunother Cancer. 2014 Dec 16;2(1):46.
- Ohlfest JR, Andersen BM, Litterman AJ, Xia J, Pennell CA, Swier LE, Salazar AM, Olin MR. Vaccine injection site matters: qualitative and quantitative defects in CD8 T cells primed as a function of proximity to the tumor in a murine glioma model. J Immunol. 2013;190(2):613-20.
- Andersen BM, Pluhar GE, Seiler CE, Goulart MR, SantaCruz KS, Schutten MM, Meints JP, O'Sullivan MG, Bentley RT, Packer RA, Thomovsky SA, Chen AV, Faissler D, Chen W, Hunt MA, Olin MR, Ohlfest JR. Vaccination for invasive canine meningioma induces in situ production of antibodies capable of antibody-dependent cell-mediated cytotoxicity. Cancer Res. 2013;73(10):2987-2997.
- Andersen BM, Ohlfest JR. Increasing the efficacy of tumor cell vaccines by enhancing cross priming. Cancer Lett. 2012;325(2):155-64.
- Olin MR, Andersen BM, Zellmer DM, Grogan PT, Popescu FE, Xiong Z, Forster CL, Seiler C, SantaCruz KS, Chen W, Blazar BR, Ohlfest JR. Superior efficacy of tumor cell vaccines grown in physiologic oxygen. Clin Cancer Res. 2010;16(19):4800-8.
- Olin MR, Andersen BM, Litterman AJ, Grogan PT, Sarver AL, Robertson PT, Liang X, Chen W, Parney IF, Hunt MA, Blazar BR, Ohlfest JR. Oxygen is a master regulator of the immunogenicity of primary human glioma cells. Cancer Res. 2011;71:6583-9.
- Walter Low
- Karen Ashe
- Kevin Wickman
Courses Taken Beyond the Core Courses:
- MICA 8011 Current Topics in Immunology
- PUBH 6414 Biostatistical Methods I
- MICA 8004 Cancer and Cell Biology
- MICA 8013 Translational Cancer Research
Graduate Level Minor:
- Walter Low
- David Largaespada
- Bruce Blazar
- Dan Kaplan
Conferences Attended and Presentations:
- American Academy of Neurology, Spring 2008
- Society for Neuroscience Annual Meeting, Fall 2009
- Society for Neuro-Oncology Annual Meeting, Fall 2010
Awards and Honors:
- Torske Klubben Fellowship for Minnesota Residents (2009-2011)
- Cancer Biology Training Grant (2011-)
- American Association of Cancer Research, Associate, 2012
- Spring, TX