1. 24-Hour Cross-Match Laboratory
24-hour Cross-Matching Laboratory, Red Cell Reference Laboratory and Platelet Reference Testing Laboratory made up of the Immunohaematology section in Blood Services Group (BSG) which provides patient-centric red cells and platelets diagnostic testing services to all hospitals in Singapore.
The 24-hour Cross Matching Laboratory operates round-the clock services for ABO and Rh type determination, pre-transfusion screening for clinically significant red cell antibody and compatibility testing for blood transfusion recipients as well as issues specialized blood products to all hospitals.
The Red Cell Reference and Platelet Reference Testing Laboratories provide specialised referral services to hospitals and clinical laboratories that encounter difficulties in red cell and platelet diagnostic investigation. The investigational services provided range Identification and characterisation of atypical antibody, red cell auto-antibody, cold antibody and resolution of ABO discrepancies as well as platelet antibody screening and identifications. The Red Cell Reference Testing Laboratory also runs the National Proficiency Testing Program for ABO/RH Typing to clinical laboratories in Singapore.
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2. Tissue Typing
The Tissue Typing Laboratory, established in 1988, provides human leukocyte antigen (HLA) typing, HLA antibody screening and lymphocyte crossmatching services. These tests are required for patients undergoing evaluation for organ transplantation and bone marrow transplantation, for patients requiring platelet transfusions from HLA-matched donors and for patients undergoing evaluation of conditions with known associations to particular HLA alleles, locally and also for patients in the region.
HLA typing is performed using both serological and molecular techniques. Typing for HLA class I antigen uses complement dependent cytotoxicity. Typing for HLA class I and class II alleles uses polymerase chain amplification with sequence-specific primers.
Antibody screening by complement dependent cytotoxicity determines whether antibody to HLA antigens is present in patient serum. Identification of antibody to HLA antigens is performed using fluorescence-activated flow cytometry. Crossmatching mixes serum from patients and lymphocytes from potential donors to test whether the patient has formed antibody to donor antigens and is performed using complement dependent cytotoxicity or flow cytometry.
HLA typing is performed using both serological and molecular techniques. Typing for HLA class I antigen uses complement dependent cytotoxicity. Typing for HLA class I and class II alleles uses polymerase chain amplification with sequence-specific primers.
Antibody screening by complement dependent cytotoxicity determines whether antibody to HLA antigens is present in patient serum. Identification of antibody to HLA antigens is performed using fluorescence-activated flow cytometry. Crossmatching mixes serum from patients and lymphocytes from potential donors to test whether the patient has formed antibody to donor antigens and is performed using complement dependent cytotoxicity or flow cytometry.
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3. Cell Processing Laboratory and Research
The Cellular Therapy Programme at HSA is committed to the development of translational novel cellular therapies for the treatment of diseases, such as cancer, autoimmune diseases, and diabetes. The Cell Processing Laboratory (CPL), which fulfills Good Tissue Practices (GTP)/ Good Manufacturing Practices (GMP) requirements, was officially commissioned in 2006. The CPL is a research and translational service laboratory that provides cellular product processing for collaborative clinical trials that require GTP/ GMP conditions. Stringent regulatory standards ensure consistent quality and purity/ sterility of manufactured cellular products for safe application to patients. Current productions include ‘cytokine induced killer cells', CIK or NK-like T cells, which are infused into patients suffering from haematological malignancies, such as leukemia and lymphoma, in a Phase I/II clinical trial.
The staff working in the GMP facility are well versed in the stringent processes required to run the lab including ensuring that air pressure gradients are maintained and thresholds of particulate matter not exceeded. All products manufactured are subject to release criteria consistent with other international labs. The staff have all been trained in international labs of excellence overseas.
Basic and translational research projects with emphasis on natural killer (NK) cells as potentially powerful candidates for cancer immunotherapy are conducted in the support laboratories. NK cells are innate immune system cells, hence their cytotoxic response is immediate, does not require prior immunization, and potentially targets a broad range of malignancies. Our current projects are designed to generate NK cells with superior potency to improve NK mediated adoptive immunotherapy against cancer. For example we study highly cytolytic human CD56+CD8+ NK subset cells compared to less cytotoxicCD56+CD8- subset cells to identify molecules and mechanisms that are linked to enhanced NK cytotoxicity. It is conceivable that targeted modifications to the signaling pathways of cytotoxicity of endogenous NK cells will lead to the generation of NK cells with even greater efficacy in the future. In other projects we investigate effects of different NK activation modes, such as novel cytokines and neuropeptides to enhance NK proliferation and/or functionality for potential future clinical applications involving the CPL.
Primary NK cells attack tumour targets (K562, cells shown in red) (Confocal Microscopy Images) | Tumour targets induce cytolytic granule polarization - NK cell line NK-92 attacks K562 (shown in green) (Confocal Microscopy Images) |
Selected Publications:
Suck, G., Branch, D. R., Aravena, P., Mathieson, M., Helke, S., and Keating, A., 2006. Constitutively polarized granules prime KHYG-1 natural killer cells. International Immunology 18(9):1347-1354.
Suck, G., 2006. Novel approaches for using natural killer cells in cancer cell therapy. Seminars in Cancer Biology 16 (5):412-418.
Suck G. Natural killer cell activation. Encyclopedia of Cancer
Book Essay. Second Edition Cancer Encyclopedia, Springer. Schwab, Manfred (Ed.)
2nd ed., 2009, LXXXVII, 3235 p. 979 illus. In 4 volumes. ISBN: 978-3-540-36847-2.
Koh, M. B. C., Goh, T. Y., Tan, P. H. C., Koh, L. P., Hwang, W. Y. K., Loh, Y., Tan, D., Ng, H. J., Chuah, C., Lim, T. J., Niam, M., Suck, G., Chan, M., Phang C. Y., Lee, J. J., Wee, V., Ng, H. Y., Lim, C. H., Yiu, R, Kam, G., Ang, A., and Linn, Y. C. 2008. Stem Cell Transplant Programme at the Singapore General Hospital. Bone Marrow Transplant, 42 Suppl 1:S121-S124.
Linn, Y. C., Lim, T. J., Niam, M., Suck, G., Goh, Y. T., Hwang, W., Loh, Y., Ng, L. H., Yong, H. X., and Koh, M. B. C., 2008. Cytokine Induced Killer Cells are feasible and safe for both autologous and allogeneic applications in patients with haematological malignancies. Abstract 2917. Blood. In press.
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