JOURNAL OF EVOLUTIONARY MEDICINE Allogeneic cell therapy as potential cure of hematologic malignancies Shimon Slavin Biotherapy International Ltd, Israel Abstract In sharp contrast to existing immunotherapy procedures based on ac- tivation of patient’s own immune system, our working hypothesis was Biography that optimal induction of immunotherapy may be accomplished using Shimon Slavin, MD, Professor of Medicine, pioneered the use of personalized intentionally mismatched activated donor lymphocytes as the most anti-cancer immunotherapy mediated by donor lymphocytes and innovative effective approach for elimination of fully resistant malignant cells methods for stem cell transplantation for cure of malignant and life-threatening by a mechanism resembling rejection of an allograft. Using murine B non-malignant disorders, including treatment of autoimmune diseases and in- cell leukemia (BCL1) and based on their pilot clinical experience, they duction of transplantation tolerance to bone marrow and organ allografts. More proved that effective graft-vs-leukemia (GVL) effects following SCT and recently, he pioneered the use of multi-potent mesenchymal stromal cells for durable engraftment of donor lymphocytes could eliminate otherwise multi-system regenerative medicine. He is the author of four books, >660 sci- entific publications and serves on many Editorial Boards and many national and incurable heavy tumor burden but at the risk of severe GVHD. Accord- international advisory boards. He received many international awards in recog- ingly, they developed an immunotherapy protocol based on the use nition of his contributions for treatment of cancer and non-malignant disorders. of non-engrafting, Intentionally mismatched activated Killers (IMAK) activated in vitro for five days with IL-2 prior to cell infusion with five Publications days activation in vivo following cell infusion with no prior SCT. They confirmed that curative GVL was induced by IMAK with no risk of GVHD 1. Slavin S, Naparstek E, Nagler A, Ackerstein A, Kapelushnik J, Or R (Dec 1995). “Allogeneic cell therapy for relapsed leukemia after bone marrow due to consistent rejection of mismatched donor lymphocytes treated transplantation with donor peripheral blood lymphocytes”. Experimental at the stage of minimal residual disease (MRD), elimination of leukemia Hematology. 23 (14): 1553–62. PMID 8542946 and cure were accomplished by transient circulation of alloreactive do- 2. Naparstek E, Or R, Nagler A, Cividalli G, Engelhard D, Aker M, Gimon Z, nor lymphocytes consisting of T & NK cells combined, indicating that Manny N, Sacks T, Tochner Z, Weiss L, Samuel S, Brautbar C, Hale G, Wald- “the last” cancer cell was eliminated since even residual of 10 BCL1 mann H, Steinberg SM, SLAVIN S (March 1995). “T-cell-depleted alloge- cells can result in lethal leukemia. Using IMAK following non-myeloab- neic bone marrow transplantation for acute leukaemia using Campath-1 lative conditioning in parallel with suppression of regulatory T cells by antibodies and post-transplant administration of donor’s peripheral blood cyclophosphamide and using alpha interferon for induced expression lymphocytes for prevention of relapse”. British Journal of Haematology. 89 (3): 506–515. doi:10.1111/j.1365-2141.1995.tb08356.x of cancer antigens, their first multiple myeloma patients as well as our 3. Slavin S (August 2001). “Immunotherapy of cancer with alloreactive first patient with AML and two with NHL remain disease free >25 years. lymphocytes”. The Lancet Oncology. 2 (8): 491–498. doi:10.1016/S1470- Long-term progression-free survival was also reported in other pa- 2045(01)00455-7 tients with hematologic malignancies and even solid tumors since then 4. Tangnararatchakit K, Tirapanich W, Anurathapan U, Tapaneya-Olarn W, but cure of cancer by IMAK depends exclusively on clinical application Pakakasama S, Jootar S, Slavin S, Hongeng S (May 2012). “Depletion of of successful immunotherapy at the stage of minimal residual disease. alloreactive T cells for tolerance induction in a recipient of kidney and he- matopoietic stem cell transplantations”. Pediatr Transplant. 16 (8): E342– E347. doi:10.1111/j.1399-3046.2012.01701.x 5. Prigozhina TB, Gurevitch O, Zhu J, Slavin S (May 1997). “Permanent and specific transplantation tolerance induced by a nonmyeloablative treat- ment to a wide variety of allogeneic tissues: I. Induction of tolerance by a short course of total lymphoid irradiation and selective elimination of the donor-specific host lymphocytes”. Transplantation. 63 (10): 1394–1399. doi:10.1097/00007890-199705270-00004 6. Slavin S (Jul 1993). “Depletion of donor-reactive cells as a new concept for improvement of mismatched bone marrow engraftment using re- duced-intensity conditioning”. Bone Marrow Transplantation. 12 (1): 85–8. PMID 8104072 5th International Conference on Clinical Hematology and Transfusion Medicine | Rome, Italy | February 24-25, 2020 Abstract Citation: Shimon Slavin, Allogeneic cell therapy as potential cure of hematologic malignancies, Global Hematology 2020, 5th Interna- tional Conference on Clinical Hematology and Transfusion Medicine, Rome, 24-25 February, 2020, 01 Journal of Evolutionary Medicine | 2020 ISSN: 2471-9455 Volume 8 | Issue 3 | 01.