Allogeneic Cytokine-induced Killer Immunotherapy for Relapse After Allogeneic Marrow Transplant for Haematological Malignancies

Summary

Cytokine-induced killer ( CIK ) cells have been shown by our lab to be cytolytic against both autologous and allogeneic acute myeloid leukemia ( AML ) cells. Large scale expansion of CIK cells has also been shown to be feasible in healthy allogeneic stem cell donors as well as in patients undergoing mobilization for autologous transplant. Donor lymphocyte infusion (DLI) has been shown to be active against some haematological malignancies including CML, AML, MDS,NHL and Hodgkin's disease. These donor lymphocytes can be further activated in vitro to become CIK cells. At least 2 other centers in the world have given allogeneic CIK cells for patients relapsing post allogeneic transplant for a variety of haematological malignancies. These early reports have demonstrated feasibility, absence of increased GVHD and possible efficacy in some cases. We are proposing a Phase I /II study on the feasibility / efficacy of immunotherapy with allogeneic CIK cells for patients who relapse after allogeneic marrow transplant for their haematological malignancies. These patients have to be either refractory to conventional donor lymphocyte infusion, or need a larger number of donor lymphocyte than could be provided by unmanipulated donor lymphocytes. Donor lymphocytes will be collected and cultured in GMP facilities to maturity, then infused into patients. This will be given in graded doses at 4 weekly intervals and continued on in the absence of GVHD till remission is achieved or disease progression occurs. Patients may receive various forms of chemotherapy appropriate to the clinical condition in each case before the allogeneic CIK infusion. Efficacy will be assessed by comparing the response to allogeneic CIK infusion vs that to due to conventional DLI, ie response to the two different treatment using DLI response as the comparator. We expect about 10 such cases to be done over the next 3 years. Significant statistics is unlikely to be generated but observation and description of the response can generate useful information for presence or not of the efficacy of such a treatment. If clinical efficacy and superiority over conventional DLI is demonstrated, then future allogeneic CIK may take the place of DLI in this group of poor prognosis patients who relapse after allogeneic transplant .

Timeline

Start

2006-08

Primary completion

2012-12

Completion

2012-12

Publications

• Background 1. YC Linn, LC Lau, KM Hui Generation of cytokine-induced killer cells from leukemic samples with in vitro cytotoxicity against autologous and allogeneic leukemic blasts British Journal of Haematology, 2002, 116: 78-86 2. C Sheffold, M Edinger, R S Negrin A Phase I trial of autologous cytokine-indueced killer cells for transplant of relapsed Hodgkin's disease and Non Hodgkin's lymphoma Biol of Blood and Marrow Transplant 2005, 11:181-187 3. Hao Jiang, Kaiyan Liu, Chunrong Tong, Bin Jiang, Daopei Lu The efficacy of chemotherapy in combination with autologous cytokine-induced killer cellsi n acute leukemia Chinese J Internal Med 2005, 44(3): 198-201 4. Jeanette Baker, Michael R Vernais, Maki Ito et al Expansion of cytolytic CD8+ natural killer T cells with limited capacity for graft-versus- host disease induction due to interferon gamma productin Blood, 2001, 97(!)(: 2923-2931 5. Ginna G Laport, Kevin Sheehan, Robert Lowsky et al Cytokine Induced Killer (CIK) cells as post transplant immunotherapy following allogeneic haemopoietic cell transplantation (Oral session ) Blood 2006, 108 (11) #412 6.Martino Introna, Gianmaria Borleri, Elena Conti et al Infusion of donor derived Cytokine-induced Killer Cells may induce clinical remission with limited GVHD in patients relapsing after allogeneic stem cell transplantation ( poster session) Blood 2006, 108(11), #3698 7. David L Porter, Bruce L Levine, Nancy Bunin et al A phase I trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation Blood 2006, 107 (4), 1325-1331

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