Kunle Odunsi, M.D., Ph.D. Division of Gynecologic Oncology Co-Leader, Tumor Immunology and Immunotherapy Program Roswell Park Cancer Institute Buffalo, NY

Women diagnosed with advanced-stage ovarian cancer may respond positively to chemotherapy, but the benefits seldom last. More than seventy percent die of recurrent disease within five years.

With the help of the CRI Clinical Investigation Program, Dr. Kunle Odunsi is able to focus his talents on improving those odds through immunotherapy.

Many ovarian-cancer patients in his CRI/LICR Cancer Vaccine Collaborative clinical trials at Roswell Park Cancer Institute in Buffalo, NY, show encouraging results, including significant delays in time to disease recurrence and, in some cases, remission.

The Nigerian-born physician scientist has also made major contributions to monitoring patients’ immune responses during vaccine therapy and arriving at accurate prognoses. He’s published more than eighty scientific papers on the subject.

Most recently, Dr. Odunsi and colleagues have recently identified a number of potential biomarkers in ovarian cancer. The identified proteins appear to play a critical role in ovarian cancer progression and may well serve as a predictive marker for early detection of the disease.

Dr. Odunsi is as comfortable with patients as he is with Petri dishes. "He takes time to explain the science and makes me feel like a participant in something bigger than just what’s happening to me," says one clinical trial patient. "He’s brilliant and compassionate."

Physician scientists like Dr. Odunsi are bridging the divide between the laboratory and the clinic, translating basic discoveries into new therapies—and new hope—for cancer patients.

Click here to read more about Dr. Odunsi's research.

More on ovarian cancer at CRI:

	Sophie Stenbeck, a young philanthropist and heiress to the Stenbeck media fortune, tragically lost her mother to ovarian cancer. Out of her family's devastating loss came a passionate desire to help researchers find new ways to detect and treat the disease.
	Christine Sable is a wife and mother of two. At age 44, she was diagnosed with late-stage ovarian cancer. After surviving the rigors of chemotherapy and surgery, she opted to participate in a Cancer Vaccine Collaborative clinical trial of an ovarian cancer vaccine. She recently celebrated her 50th birthday, still cancer free.

Kunle Odunsi, M.D., Ph.D.
Source: Roswell Park Cancer Institute 

Dr. Kunle Odunsi joined the staff of Roswell Park Cancer Institute (RPCI) in 2001 as an attending surgeon in the Division of Gynecologic Oncology, Department of Surgical Oncology. Dr. Odunsi earned his medical degree from the University of Ife, Ile-Ife, Nigeria, in 1984. He completed postgraduate training in obstetrics and gynecology at the Rosie Maternity and Addenbrookes Hospitals, University of Cambridge, UK, leading to membership of the Royal College of Obstetricians and Gynecologists in 1991.

Dr. Odunsi completed a research fellowship in molecular oncology and earned his Ph.D. at the Imperial Cancer Research Fund Laboratories, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, UK. Subsequently, he completed residency training in obstetrics & gynecology at the Yale University School of Medicine, New Haven, CT, and clinical fellowship in gynecologic oncology at RPCI. He is a fellow of the Royal College of Obstetricians and Gynaecologists in the United Kingdom. He is also a fellow of the American College of Obstetricians and Gynecologists.

Dr. Odunsi is licensed by New York State and certified in obstetrics & gynecology by the American Board of Obstetrics and Gynecology. He is also board certified in the sub-specialty of gynecologic oncology.

Dr. Odunsi’s research interests include the molecular characterization of tumor antigens in ovarian cancer and their application to the development of vaccine therapies for the disease. He is the co-leader of the Tumor Immunology and Immunotherapy Program at Roswell Park Cancer Institute. He is also the director of the U.S. operations of the Cancer Vaccine Collaborative, a joint program of the Cancer Research Institute and Ludwig Institute for Cancer Research, and is director of the Cancer Research Institute Ovarian Cancer Working Group, a program of the CRI Coordinated Cancer Initiatives. Dr. Odunsi is also program leader of the Cancer Research Institute Cancer Vaccine Consortium's ImmunoAssay Proficiency Panel Program.

Dr. Odunsi is a member of the American Association for Cancer Research, the American Society of Clinical Oncology, American Society for Reproductive Immunology, Association of African Biomedical Scientists, Cooperative Ovarian Cancer Group for Immunotherapy, Gynecologic Oncology Group, Society for Experimental Biology and Medicine, Society for Gynecologic Investigation, and the Society of Gynecologic Oncologists.

Dr. Odunsi has authored or co-authored more than 80 journal publications, book chapters and abstracts. He also is an ad hoc reviewer for the American Journal of Obstetrics and Gynecology, BMC Cancer, Cancer Immunity, Cancer Immunology Immunotherapy, Cancer Letters, Cancer Research, Clinical Cancer Research, Expert Opinion on Biological Therapy, Fertility and Sterility, Gynecologic Oncology, International Journal of Cancer, Journal of Clinical Pathology, Journal of the Society for Gynecologic Investigation, the Lancet, Molecular Cancer Therapeutics, Oncogene, Oncology and the Proceedings of the National Academy of Sciences, U.S.A.

RESEARCH SUMMARY

Ovarian Cancer Immunotherapy Program: The long-range goal of our studies is to harness the potential of cellular immune responses for improving the outcome for patients with epithelial ovarian cancer (EOC). While the majority of women with advanced stage ovarian cancer respond to first-line chemotherapy, most of these responses are not durable and more than 70% of patients die of recurrent disease within 5 years of diagnosis.

This has stimulated interest in the development and application of alternative therapeutic strategies for the disease. Among them, immunotherapy has attracted considerable interest in recent years because of major progress in the identification of human tumor antigens (TA) suitable for clinical use. However, considerable obstacles to the development of effective immunotherapy exist including inability to (i) induce expansion of large pools of antigen specific CD8+ T cells (ii) maintain durable anti-tumor immunity (iii) overcome inherent tolerogenic mechanisms, such as CD4+CD25+ regulatory T cells (Tregs).

In our preliminary studies, we have shown (i) improved clinical outcomes are associated with increased frequency of intraepithelial CD8+ tumor infiltrating T cells in human EOC  (ii) the beneficial prognostic effect of CD8+ TIL is modulated by CD25+FOXP3+ subpopulation of CD4+ T cells with immunosuppressive properties. Therefore, the development of strategies to enhance the potential of tumor-antigen specific CD8+ T cells is urgently needed for extending remission rates in this disease. These strategies should attempt to prime robust CD8+ T cell expansion, promote durable anti-tumor immunity and counteract the immunosuppressive conditions produced by Tregs in order to reveal greater anti-tumor immunity.

Research efforts are currently focused on the following

1. Characterization of the ovarian cancer immunome i.e. the repertoire of antigens capable of inducing immune responses in ovarian cancer . We have found NY-ESO-1 antigen to be a promising target for immunotherapy in ovarian cancer .
2. Mechanisms by which Tregs impact ovarian tumors in an in-vivo model.
3. We have completed accrual to a phase I clinical trial of immunization with NY-ESO-1DP4 p157-170 (NY-ESO-1DP4), a peptide of potential dual MHC class I and class II specificities, in patients with epithelial ovarian, fallopian tube or primary peritoneal carcinoma whose tumors express NY-ESO-1 or LAGE-1.  We are currently conducting Phase II study of recombinant vaccinia-NY-ESO-1 (rV-NY-ESO-1) and recombinant fowlpox-NY-ESO-1 (rF-NY-ESO-1) in patients with epithelial ovarian, fallopian tube or primary peritoneal carcinoma whose tumors express NY-ESO-1 or LAGE-1 antigen.
4. Ovarian cancer detection using 1H-NMR metabonomics: We recently conducted a pilot study to evaluate the utility of using 1H-NMR-based metabonomic analysis to discriminate samples from women with EOC from healthy controls, and women with benign ovarian diseases. Metabonomics is based on the use of NMR (and other spectroscopic methods) and multivariate statistics for biochemical data generation and interpretation. Our data indicate that the sera from patients with and without disease could be accurately identified using principal components analysis (PCA), soft independent modeling of class analogy (SIMCA), probabilistic neural networks (PNNs) and receiver operator characteristic curve analysis (ROC). Discrimination by ROC analysis was found at the 1H-NMR regions 2.77ìs and 2.04ìs from the origin (AUC of ROC curve=1.0)
5. We have continued to evaluate metabonomics in patients with stages I and II disease, and patients at high risk of ovarian cancer (from the Gilda Radner Familial Ovarian Cancer Registry, Buffalo).

Selected Papers

• Odunsi K, Qian F, Matsuzaki J, Mhawech-Fauceglia P, Andrews C, Hoffman EW, Pan L, Ritter G, Villella J, Thomas B, Rodabaugh K, Lele S, Shrikant P, Old LJ, Gnjatic S. Vaccination with an NY-ESO-1 peptide of HLA class I/II specificities induces integrated humoral and T-cell responses in ovarian cancer. Proc Natl Acad Sci U S A. 2007. In Press.
• Sato E, Olson SH, Ahn J, Jungbluth AA, Frosina D, Bundy B, Qian F, Gnjatic S, Ambrosone C, Kepner J, Keitz B, Odunsi T., Ritter G, Lele S, Chen Y, Ohtani H, Old LJ, Odunsi K. Intraepithelial CD8+ Tumor infiltrating lymphocytes and high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A. 2005;102:18538
• Odunsi K, Jungbluth A, Stockert E, Qian F, Gnajtic S, Tammela J, Intengan M, Beck A, Keitz B, Santiago D, Williamson B, Scanlan MJ, Ritter G, Chen YT, Driscoll D, Sood A, Lele S, Old LJ. NY-ESO-1 and LAGE-1 cancer-testis antigens are potential targets for immunotherapy in epithelial ovarian cancer. Cancer Res. 2003;63:6076.
• Tammela J, Jungbluth AA, Qian F, Santiago D, Scanlan M, Keitz B, Driscoll D, Rodabaugh K, Lele S, Old LJ, Odunsi K. SCP-1 “Cancer / Testis” antigen is a prognostic indicator and a candidate target for immunotherapy in epithelial ovarian cancer. Cancer Immun. 2004; 4:10.
• Sharma S, Qian F, Driscoll D, Scanlan MJ, Skipper J, Rodabaugh KJ, Lele S, Old LJ, Odunsi K. A-kinase anchoring protein 3 messenger rna expression correlates with poor prognosis in epithelial ovarian cancer. Gynecol Oncol. 2005;99:183.
• Odunsi K, Wollman R, Ambrosone C, Hutson A, McCann S, Tammela J, Geisler JP, Miller G, Sellers T, Cliby W, Qian F, Keitz B, Intengan M, Lele S, Alderfer JL. Detection of epithelial ovarian cancer using ¹H-NMR- based metabonomics. Int J Cancer. 2005;113:782.
• Li Q, Eppolito C, Odunsi K, Shrikant P. IL-12-Programmed long-term CD8+ T responses require STAT4. J Immunol. 2006;177:7618.
• Fisher D, Chen Q, Appenheimer M, Skitzki J, Wang W-C, Odunsi K, Evans S. Hurdles to Lymphocyte Trafficking in the Tumor Microenvironment: Implications for Effective Immunotherapy. Immunol Invest. 2006;35:251.
• Valmori D, Qian F, Ayyoub M, Renner C, Merlo A, Gjnatic S, Stockert E; Driscoll D, Lele S, Old LJ, Odunsi K. Expression of SSX antigen in epithelial ovarian cancer and identification of SSX-4 epitopes recognized by CD4+ cells. Clin Cancer Res. 2006;12(2)398.
• Sabbatini P, Dupont J, Aghajanian C, Derosa F, Poynor E, Anderson S, Hensley M, Livingston P, Iosonos A, Spriggs D, McGuire W, Reinartz S, Schnieder S, Grande C, Lele S, Rodabaugh K, Kepner J, Ferrone S, Odunsi K.Phase I study of the antibody abagovomab in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Clin Cancer Res. 2006;12:5503-10.
• Nishikawa H, Qian F, Tsuji T, Ritter G, Old LJ, Gnjatic S, Odunsi K. Influence of CD4⁺CD25⁺ regulatory T cells on low/ high-avidity CD4⁺ T cells following peptide vaccination. J Immunol. 2006;176:6340-6.