Journal of Blood Disorders & Transfusion

Immunotherapy of hematologic malignancies and metastatic solid tumors in experimental animals and man

2^nd International Conference on Hematology & Blood Disorders

September 29-October 01, 2014 DoubleTree by Hilton Baltimore-BWI Airport, USA

Shimon Slavin

Keynote: J Blood Disorders Transf

Abstract:

Engraftment of T cells or donor lymphocyte infusion (DLI) following allogeneic stem cell transplantation (SCT) results in graft-vs.-tumor effects (GVT) but is accompanied by acute and chronic graft-vs.-host disease (GVHD). GVT effects post SCT can be accomplished by IL-2 activated natural killer (NK) cells prepared by negative selection of CD3+ T cells or by positive selection of CD56+ NK cells. Interestingly, mismatched NK cells are much more effective GVT inducers, yet they cause no GVHD. Based on animal experiments using murine models of B cell leukemia (BCL1) and metastatic breast cancer (4T1) we have documented that GVT effects mediated by intentionally mismatched IL-2 activated killer cells (IMAK), including T, NK & NKT cells, can result in cure when applied at the stage of minimal residual disease (MRD) following conventional or high dose chemotherapy and SCT. Using IMAK with no prior SCT results in consistent rejection of alloreactive donor lymphocytes within one week and as such GVHD is prevented while malignant cells are being attacked as long as donor lymphocytes circulate. More selective GVT effects induced by IMAK against residual malignant cells can be accomplished by targeting killer T, NK & NKT cells against tumor cells by monoclonal or bispecific antibodies against over-expressed antigens (e.g. Erbitux, Avastin or Catumaxomab for solid tumors or MabThera for B cell malignancies). In conclusion, based on observations in mice and man, IMAK provides a safe treatment for patients with residual malignant cells resistant to available anti-cancer agents while avoiding the risk of GVHD.

Biography :

Shimon Slavin, MD, Professor of Medicine is currently serving as the Medical & Scientific Director of the International Center for Cell Therapy & Cancer Immunotherapy (CTCI), Tel Aviv, Israel. He pioneered the use of immunotherapy mediated by donor lymphocytes and innovative methods for stem cell transplantation for malignant and non-malignant disorders including treatment of autoimmune diseases and more recently, using multi-potent stem cells for regenerative medicine. He authored 4 books, 660 scientific publications and serves on many editorial boards and many national and international advisory boards. He received many international awards in recognition of his contributions for treatment of malignant and non-malignant disorders.