Clinical Services

Translational Trials Development and Support Laboratory (TTDSL)

Specialized Clinical Testing

The Translational Trials Development and Support Laboratory (TTDSL) is accredited by the College of American Pathologists (CAP). This accreditation documents that the laboratory not only meets Clinical Laboratory Improvement Amendments (CLIA) standards, but exceeds them. TTDSL compliance with these standards assures that test results used for decisions in routine clinical settings and for clinical trial participant eligibility and monitoring are reproducible, objective, valid, and reliable.

The current assay compendium includes the following:

  • Endotoxin by LAL
  • Hematopoietic stem cell Colony Forming Unit enumeration and collection for further analysis
  • Quantitation of VEGF-D in human serum for Lymphangioleimyomatosis (LAM) diagnosis

Please download and submit the Clinical Requisition Form if you are interested in ordering these tests. Additionally download and submit the “VEGF-D Specimen Shipping Instructions” document if ordering VEGF-D testing.

Clinical Assay Development

One of our mandates is to help investigators bring their specialized laboratory-developed tests to the clinic. We provide support in optimizing a Standard Operating Procedure (SOP), validating the assay at a level congruent with CAP regulations, and then offering the test through the TTDSL or in conjunction with another CCHMC clinical laboratory. Previous examples of this process include our Fanconi anemia complementation assay (now offered at the research level) and the VEGF-D assay.

Contact us to learn how we can help bring your assay to the clinic or prepare it for clinical trial use.

Clinical Trial Monitoring

The TTDSL has effectively supported 11 Phase I/II gene therapy clinical trials by designing tailored analytical assays and acquiring Sponsor-developed assays via Technology Transfer. We have extensive experience in providing the following services:

  • Central laboratory coordination
  • Peripheral blood leukocyte isolation, lineage sorting, and analysis by flow cytometry
  • Vector copy number by qPCR
  • Hematopoietic cell colony forming unit (CFU) assay
  • Protein HPLC
  • Gene expression by qPCR or flow cytometry
  • Replication competent vector testing by qPCR (inquire for availability)

Although these techniques have been utilized primarily for lentiviral/retroviral vector monitoring, they can be developed for any vector system or even non-gene therapy clinical trials. Testing for Phase III clinical trials is possible if satisfied by compliance with CAP regulations. Contact us to find out how we can support your clinical trial.

Selected References

1.  Chandra S, Levran O, Jurickova I, Maas C, Kapur R, Schindler D, Henry R, Milton K, Batish SD, Cancelas JA, Hanenberg H, Auerbach AD, Williams DA. (2005) A rapid method for retrovirus-mediated identification of complementation groups in Fanconi anemia patients. Mol Ther. 12(5):976-84

 2.  Kelly PF, Radtke S, von Kalle C, Balcik B, Bohn K, Mueller R, Schuesler T, Haren M, Reeves L, Cancelas JA, Leemhuis T, Harris R, Auerbach AD, Smith FO, Davies SM, Williams DA (2007). Stem cell collection and gene transfer in Fanconi anemia. Mol Ther.15(1):211-9

 3.  Zhang X, Shang X, Guo F, Murphy K, Kirby M, Kelly P, Reeves L, Smith FO, Williams DA, Zheng Y, Pang Q (2008). Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A. Blood 112(5):1683-6. Epub 2008 Jun 18

4.  Singh TR, Bakker ST, Agarwal S, Jansen M, Grassman E, Godthelp BC, Ali AM, Du CH, Rooimans MA, Fan Q, Wahengbam K, Steltenpool J, Andreassen PR, Williams DA, Joenje H, de Winter JP and Meetei AR (2009). Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M. Blood 114(1):174-80

5.  Ali AM, Kirby M, Jansen M, Lach FP, Schulte J, Singh TR, Batish SD, Auerbach AD, Williams DA, Meetei AR. (2009) Identification and characterization of mutations in FANCL gene: a second case of Fanconi anemia belonging to FA-L complementation group. Hum Mutat. 30(7):E761-70

6.  Hartmann L, Neveling K, Borkens S, Schneider H, Freund M, Grassman E, Theiss S, Wawer A, Burdach S, Auerbach AD, Schindler D, Hanenberg H, Schaal H. Correct mRNA processing at a mutant TT splice donor in FANCC ameliorates the clinical phenotype in patients and is enhanced by delivery of suppressor U1 snRNAs (2010). Am J Hum Genet. 87(4):480-93