פרופ' מיכל בסר

קורות חיים

1996-2000         דוקטוראט, חוג לאימונולוגיה, אונ' מינכן, גרמניה

2001-2004         פוסט דוקטוראט, נוירוביולוגיה מכון ויצמן

היום - 2004       מנהלת מעבדה, מכון אלה, בית חולים שיבא 

היום - 2009        מרצה, מיקרוביולוגיה קלינית ואימונולוגיה, סאקלר, אונ' ת''א.

In the past decades the increasing knowledge in cellular immunology and tumor-host immune interactions, led to the development of immunotherapy approaches. Immunotherapy, based on Adoptive Cell Transfer (ACT) of ex vivo activated and expanded Tumor Infiltrating T lymphocytes (TIL), is currently one of the most effective treatments for advanced melanoma patients. The Ella Institute at the Sheba Medical Center is one of the leading cancer centers applying TIL therapy today and our laboratory has the most advanced research in this field.

The main research focus of our laboratory is to identify predictive markers for clinical response with the aim (1) to improve the response rate of TIL therapy or (2) to select patients upfront, who are most likely to benefit from the treatment. In addition, we validate the combinational effects of TIL with immune check point inhibitors and test the effectiveness of TIL in cancers, other than melanoma.

List of Publications (Last 5 years):

1. M.J. Besser, E. Schallmach, K. Oved, A.J. Treves, G. Markel, Y. Reiter, J. Schachter . Modifying IL-2 concentrations during culture improves function of T-cells for adoptive immunotherapy. Cytotherapy. 11:206-217, 2009

2. G. Markel, R. Seidman, Y. Cohen, M.J. Besser, T.C. Sinai, A.J. Treves, A. Orenstein, R. Berger, J. Schachter. Dynamic expression of protective CEACAM-1 on melanoma cells during specific immune attack. Immunology. 126:186-200, 2009

3. G. Markel, T. Cohen-Sinai, M.J. Besser, K. Oved, A.J. Treves, E. Freidman, Y. Keisari, Z. Dotan, J. Ramon, J. Schachter. Preclinical evaluation of adoptive cell therapy for patients with metastatic renal cell carcinoma. Anticancer Res. 29:145-154, 2009

4.  M.J. Besser, R. Shapira-Frommer, A.J. Treves, D. Zippel, O. Itzhaki, E. Schallmach, A. Kubi, B. Shalmon, I. Hardan, R. Catane, E. Segal, G. Markel, S. Apter, A. Ben Nun, I. Kuchuk I, A. Shimoni, A. Nagler, J. Schachter. Minimally-cultured or selected autologous tumor infiltrating lymphocytes following a lymphodepleting chemotherapy regimen in metastatic melanoma patients. J Immunother. 32:415-423, 2009

5. G. Markel, R. Seidman, M.J. Besser, N. Zabari, R. Ortenberg, R. Shapira, A.J. Treves, R. Loewenthal, A. Orenstein, A. Nagler, J. Schachter. Natural Killer lysis receptor (NKLR)/NKLR-ligand matching as a novel approach for enhancing anti-tumor activity of allogeneic NK Cells. PLoS ONE. 4:e5597, 2009

6. K. Oved, E. Eden, M. Akerman, R. Noy, R. Wolchinsky, O. Izhaki, E. Schallmach, A. Kubi, N. Zabari, J. Schachter, U. Alon, Y. Mandel-Gutfreund, M.J. Besser*, Y. Reiter* (*corresponding authors). Featured article: Predicting and controlling the reactivity of immune cell populations in cancer. Mol Syst Biol. 5:265, 2009

Selected for "Editors' Choice": Highlights of the recent literature. 2009. Science. 324:569.

7. L. Hershkovitz, J. Schachter, A.J. Treves, M.J. Besser. Focus on adoptive T cell transfer trials in melanoma. Clin Devel Immunol. e2010:260267, 2010

8. G. Markel, R. Ortenberg, R. Seidman, S. Sapoznik, N. Koren-Morag, M.J. Besser, J. Bar, R. Shapira, A. Kubi, G. Nardini, A. Tessone, A.J. Treves, E. Winkler, A. Orenstein, J. Schachter. Systemic dysregulation of CEACAM1 in melanoma patients. Cancer Immunol Immun. 59:215-230, 2010

9. M.J. Besser, R. Shapira-Frommer, A.J. Treves, D. Zippel, O. Itzhaki, L. Hershkovitz, D. Levy, A. Kubi, E. Hovav, N. Chermoshniuk, B. Shalmon, I. Hardan, R. Catane, G. Markel, S. Apter, A. Ben-Nun, I. Kuchuk, A. Shimoni, A. Nagler, J. Schachter. Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients. Clin Cancer Res. 16:2646–2655, 2010

10. O. Itzhaki, E. Hovav, Y. Ziporen, D. Levy, A. Kubi, D. Zickich, L. Hershkovitz, A.J. Treves, B. Shalmon, G. Markel, J. Schachter, M.J. Besser. Establishment and large-scale expansion of minimally-cultured “Young” Tumor Infiltrating Lymphocytes (TIL) for adoptive transfer therapy.  J Immunother. 34:212-220, 2011.

11. E. Greenberg, L. Hershkovitz, O. Itzhaki,  S. Hajdu, Y. Nemlich, R. Ortenberg, N. Gefen, L. Edry,  I. Barschak, Y. Keisari, M.J. Besser, J. Schachter, N. Shomron, G. Markel. Regulation of cancer aggressive features in melanoma cells by microRNA molecules. PlosOne. 6:e18936, 2011

12. C.J. Shu, P. Kvistborg, B. Heemskerk, M. Fankhauser, C. Albæk Thrue, M. Toebes, N. van Rooij, C. Linnemann, M. van Buuren, J.H.M. Urbanus, J.B. Beltman, P. thor Straten, Y.F. Li, P.F. Robbins, M.J. Besser, J. Schachter, G.G. Kenter, M.E. Dudley, S.A. Rosenberg, J.B.A.G. Haanen, S. Reker Hadrup, T.N.M. Schumacher. TIL therapy broadens the tumor-reactive CD8+ T cell compartment in melanoma patients. OncoImmunol. 1(4):409-418, 2012

13. S. Sapoznik, O. Hammer, R. Ortenberg, M.J. Besser, T. Ben-Moshe, J. Schachter, G. Markel.  Novel anti-melanoma immunotherapies: disarming tumor escape mechanisms.  Clin Devel Immunol. doi:10.1155/2012/818214. 2012

14. D.B. Zippel, M. Besser, R. Shapira, A. Ben-Nun, D. Goitein, T. Davidson, A.J. Treves, G. Markel, J. Schachter, M.Z. Papa. Adoptive cell therapy with autologous tumor-infiltrating lymphocytes and high-dose interleukin-2 for metastatic melanoma: The surgeon's perspective. Exp Ther Med. 3(5): 898-902, 2012

15. S. Sapoznik, R. Ortenberg, G. Galore-Haskel, S. Kozlovski, D. Levy, C. Avivi, I. Barshack, C.J. Cohen, M.J. Besser, J. Schachter, G. Markel. CXCR1 as a novel target for directing reactive T cells toward melanoma: implications for adoptive cell transfer immunotherapy. Cancer Immunol Immun. 61(10):1833-1847, 2012

16. R. Ortenberg, L. Raz, L. Hershkovitch, S. Sapoznik-Danon, M.J. Besser, J. Schachter, G. Markel. Novel immunotherapy for malignant melanoma with a monoclonal antibody that blocks CEACAM1 homophilic interactions. Mol Cancer Ther. 11(6):1300-1310, 2012

17. H. Vernitsky, O. Rechavi, N. Rainy, M.J. Besser, M. Nagar, J. Schachter, Y. Lerenthal, M. Ehrlich, Y. Kloog, I. Goldstein. Ras oncoproteins transfer from melanoma cells to T cells and modulate their effector functions. J Immunol. 189(9):4361-4370, 2012

18. O. Itzhaki, E. Greenberg, B. Shalmon, A. Kubi, A.J. Treves, R. Shapira-Frommer, C. Avivi, R. Ortenberg, E. Ben-Ami, J. Schachter, M.J. Besser*, G. Markel* (*corresponding authors). Nicotinamide inhibits vasculogenic mimicry, an alternative vascularization pathway observed in highly aggressive melanoma. PlosOne. 8(2):e57160, 2013

19. M.J. Besser, T Shoham, O. Harari-Steinberg, N. Zabari, R. Ortenberg, A. Yakirevitch, A. Nagler, R. Loewenthal, J. Schachter, G. Markel. Development of allogeneic NK cell adoptive transfer therapy in metastatic melanoma patients: in vitro preclinical optimization studies. PlosOne. 8(3):e57922, 2013

20. O. Itzhaki, D. Levy, D. Zikich, A.J. Treves, G. Markel, J. Schachter, M.J. Besser.  Adoptive T-cell transfer in melanoma. Immunother. 5(1):79-90. 2013

21. Y. Nemlich, E. Greenberg, M. Ortenberg, M.J. Besser, I. Barshack, J. Jacob-Hirsch, E. Jacoby, E. Eyal, L. Rivkin, V. Prieto, N. Chakravarti, L. Duncan, D. Kallenberg, D. Bennett, N. Amariglio, M. Bar-Eli, J. Schachter, G. Rechavi, G. Markel. Fundamental cell regulation by ADAR1 enzyme is lost in metastasis by microRNAs to promote malignancy. J Clin Invest. 123(6):2703-2718, 2013

22. D. Zikich, J. Schachter, M.J. Besser. Immunotherapy for the Management of Melanoma: The Next Steps. Am J Clin Dermatol. 14(4):261-272. 2013

23. M.J. Besser, R. Shapira-Frommer, O. Itzhaki, A.J. Treves, D. Zippel, D. Levy, A. Kubi, N. Shoshani, D. Zikich, Y. Ohayon, D. Ohayon, B. Shalmon, G. Markel, R. Yerushalmi, S. Apter, A. Ben-Nun, E. Ben-Ami, A. Shimoni, A. Nagler, J. Schachter. Adoptive Transfer of Tumor Infiltrating Lymphocytes in Metastatic Melanoma Patients: Intent-to-Treat Analysis and Efficacy after Failure to Prior Immunotherapies. Clin Cancer Res. 19(17):4792-4800, 2013

24. E. Greenberg, M.J. Besser, E. Ben-Ami, R. Shapira-Frommer, O. Itzhaki, D. Zikich, D. Levy, A. Kubi, E. Eyal, A. Onn, Y. Cohen, I. Barshack, J. Schachter, G. Markel.  A comparative analysis of total serum miRNA profiles identifies novel signature that is highly indicative of metastatic melanoma. Biomarkers. 18(6):502-508, 2013

25. M.J. Besser. Author’s View: Is there a future for adoptive T cell transfer in melanoma?

OncoImmunol. 2(10):e26098. 2013