Research interests

The Melanoma and Cancer Immunotherapy Center at the Hadassah Hospital, and Lotem’s lab as the leader of the center is at the forefront of innovative research and patient treatment.  As such, the Center has a significant impact on the management of cancer patients through the development of novel approaches to improve current immunotherapies. T Cell Therapy is one such immunotherapy that represents a highly promising and robust approach for the treatment of many cancers.

During the last years, the lab has been studying the SLAM (signaling lymphocyte activation molecule) family of receptors in the anti-cancer immune response. Our data, recently published, suggests that SLAMF6 may play a role in the immune regulation of lymphocyte responses. We hypothesize that splice variants may be involved, and may, therefore, have potential significance for developing the future novel immunotherapies for cancer.

We are enthusiastic about this new direction in light of Prof. Lotem’s deep involvement with the treatment of melanoma patients with new immunotherapies just entering clinical use. It is now clear that triggering the immune system is beneficial for patients, but the success rates are still too low and the need to target more than one modulatory molecule is apparent.

Our team includes clinicians and basic and translational researchers who, in addition to extensive immunological experience, have the benefit of proximity to the clinic and immediate access to clinical data and patient-derived tissues.

Research projects

Basic and translational research

• Research into new immune checkpoint modulation using the SLAM family of immune receptors
• Investigation of alternative splicing as a regulatory mechanism of T cell function
• Models of brain metastases to overcome resistance to immunotherapy
• Bioinformatics-based study of T cell dynamics

Clinical research

• Adoptive transfer of anti-cancer lymphocytes
• Adoptive cell therapy using genetically engineered T cells
• Active vaccination against solid tumors using genetically engineered vaccines

Collaborations:

• Michal Baniyash, Faculty of Medicine, Hebrew University Jerusalem Israel.
• Rotem Karni, Faculty of Medicine, Hebrew University Jerusalem Israel.
• Ora Furman, Faculty of Medicine, Hebrew University Jerusalem Israel.
• Assaf Friedler, Institute of Chemistry, Hebrew University Jerusalem Israel.
• Cyril Cohen, Bar-Ilan University.
• Ami Navon, Department of Biological Regulation, Weizmann Institute of Science.
• Nir Hacohen, Broad institute, Boston, USA.
• Andre’ Veillette, IRCM, Montreal, Canada.
• Peter Lee, City of Hope, California, USA.
• Keren Yitzhak, Technion, Israel.

1. Hajaj E, Eisenberg G, Klein S, Frankenburg S, Merims S, Ben-David I, Eisenhaure T, Henrickson S, Villani A, Hacohen N, Abudi N, Abramovich R, Cohen J, Peretz T, Veillette A, Lotem M. SLAMF6​ deficiency augments tumor killing and skews towards an effector phenotype revealing it as a novel T cell checkpoint. eLife.(2020) 9.
2. Hadash-Bengad R, Hajaj E, Klein S, Merims S, Frank S, Eisenberg G, Yakobson A, Orevi M, Peretz T, Lotem M, Cohen J. Immunotherapy Potentiates the Effect of Chemotherapy in Metastatic Melanoma – A Retrospective Study. Frontiers in Oncology.(2020) 10.
3. Eisenberg G, Engelstein R, Geiger-Maor A, Hajaj E, Merims S, Frank S, Uzana R, Rutenberg A, Machlenkin A, Frei G, Peretz T, Lotem M. Soluble SLAMF6 Receptor Induces Strong CD8+ T-cell Effector Function and Improves Anti-melanoma Activity In Vivo. Cancer immunology research.‏ 6. 127-138 (2018).
4. Cohen J, Merims S, Frank S, Engelstein R, Peretz T, Lotem M. Adoptive cell therapy: past, present and future. Immunotherapy. 2017 Jan; 9(2):183-196.
5. Engelstein R, Merims S, Eisenberg G, Cohen J, Frank S, Hamburger T, Frankenburg S, Ron I, Isacson R, Grenader T, Steinberg H, Cohen SJ, Peretz T, Lotem M. Immune monitoring of patients treated with a whole-cell melanoma vaccine engineered to express 4-1BBL. J Immunother. 2016 Oct; 39(8):321-8.
6. Lotem M, Merims S, Frank S, Hamburger T, Nissan A, Kadouri L, Cohen JE, Straussman R, Eisenberg G, Frankenburg S, Peretz T. Autologous melanoma vaccine for macroscopic stage III disease: adjuvant role, biomarkers and improved response to CTLA-4 blockade. J Immunol Res. 2016; 2016:8121985 2016.
7. Pato A, Eisenberg G, Machlenkin A, Margalit A, Cafri G, Frankenburg S, Merims S, Peretz T, Lotem M*, Gross G*. Messenger RNA encoding constitutively active Toll-like receptor 4 enhances effector functions of human T cells. Clin Exp Immunol. 2015 Nov;182(2):220-9.
8. Uzana R, Eisenberg G, Merims S, Frankenburg S, Pato A, Yefenof E, Engelstein R, Peretz T, Machlenkin A, Lotem M. Human T cell crosstalk is induced by tumor membrane transfer. PLoSOne. 2015; Feb 11; 10(2).