We performed a Phase I/II clinical trial to study the feasibility, toxicity and efficacy of allogeneic cytokineinduced killer (CIK) cell expansion, and treatment for patients with haematological malignancies who relapsed after allogeneic haemopoietic SCT (allo-HSCT). Allogeneic CIK cells were successfully generated for a total of 24 patients, including those from patients' own leukapheresis products in 5 patients who had no access to further donor cells. The median CD3 þ T-cell expansion was 9.33 (1.3-38.97) fold, and CD3 þ CD56 þ natural killer (NK)-like T-cell expansion was 27.77 (2.59-438.93) fold. A total of 55 infusions were done for 16 patients who had either failed or progressed after initial response to various individualized chemotherapy regimens and donor lymphocyte infusion (DLI), at doses ranging from 10 to 200 million CD3 þ cells/kg. Response attributable to CIK cell infusion was observed in five patients. These included two with ALL, two with Hodgkin's disease (HD) and one with AML, and two of whom had a response sustained for more than 2 years. Acute GVHD occurred in three and was easily treatable. This study provides some evidence suggestive of the efficacy of allogeneic CIK cells even after failure of DLI in some cases.

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Novel cancer cellular therapy approaches involving long-term ex vivo IL-2 stimulated highly cytotoxic natural killer (NK) cells are emerging. However, adhesion properties of such NK cells are not very well understood. Herein, we describe the novel observation of permanently activated alphaLbeta2 integrin leukocyte function-associated antigen (LFA)-1 adhesion receptor in long-term IL-2 activated NK cells and the permanent NK cell lines KHYG-1 and NK-92. We show that such cytokine activated NK effectors constitutively adhered to the LFA-1-ligand ICAM-1, whereas binding to the lower affinity ligand ICAM-3 required additional exogenous activating conditions. The results demonstrate an extended conformation and an intermediate affinity state for the LFA-1 population expressed by the NK cells. Interestingly, adhesion to ICAM-1 or K562 induced pronounced cell spreading in KHYG-1, but not in NK-92, and partially in long-term IL-2 stimulated primary NK cells. It is conceivable that such differential adhesion characteristics may impact motility potential of such NK effectors with relevance to clinical tumor targeting. KHYG-1 could be a useful model in planning future targeted therapeutic approaches involving NK effectors with augmented functions.

The adult transplant programme at Singapore General Hospital (SGH) was established in 1985 and more than 820 transplants have been performed to date. An average of about 60 adult transplants (autologous and allogeneic) are performed each year. Transplants offered at SGH run the range from autologous to mismatched cord and unrelated transplants. Special interests of the transplant programme include non-myeloablative transplants in aplastic anaemia, cell therapy protocols including cytokine-induced killer cells, patterns of GVHD, cord blood transplantation for autoimmune diseases and graft engineering. A cGMP (good manufacturing practice) cell therapy laboratory was recently established to facilitate bench-to-bedside translational cell therapy trials. A BMT consortium has been formed among the various paediatric and adult transplant centres for harmonization of protocols and research activities.

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