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Dr Frank Waldron-Lynch

Dr Frank Waldron-Lynch

Experimental Medicine and Immunotherapeutics (EMIT)


Office Phone: 01223 762327

Research Interests

Dr Frank Waldron-Lynch is a globally trained Physician-Scientist at the University of Cambridge, where he leads an a multifunctional Experimental Medicine Team that develops novel immunotherapeutic strategies to treat and ultimately prevent autoimmune diseases in patients. The aim of this programme is to accelerate the development of immunotherapies targeted to genetically validated human disease pathways in type 1 diabetes and other autoimmune diseases.

The experimental medicine programme is focused on adaptive mechanistic clinical trials of immunotherapies. By understanding the response of the human immune system to therapy we aim to establish the correct dose and frequency prior to testing clinical efficacy in disease.

For those interested in participating in studies of type 1 diabetes, please follow the link www.clinical-trials-type1-diabetes.com to request information about eligibility and enrolment.

Keywords

pre-clinical modelling of human immunotherapy in vivo ; Experimental medicine ; Autoimmune diseases ; Adaptive trial design ; immunotherapy ; autoimmunity ; Immunotherapeutics ; biomarkers ; stratified medicine ; Medical Genetics ; translational immunology ; immunogenetics ; stratification of patients by genotype and immunophenotypes ; metabolism ; design and conduct of clinical trials of immunotherapy

Topics

  • autoimmune diseases
  • Experimental Medicine
  • Immunotherapeutics

Key Publications

Todd JA, Evangelou M, Cutler AJ, Pekalski ML, Walker NM, et al. (2016) Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial. PLOS Med 13(10): e1002139. doi: 10.1371/journal.pmed.1002139

Heywood J, Evangelou M, Goymer D, et al. Effective recruitment of participants to a phase I study using the internet and publicity releases through charities and patient organisations: analysis of the adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes (DILT1D). Trials 2015, 16:86, doi:10.1186/s13063-015-0583-7

F Waldron-Lynch, P Kareclas, K Irons et al. Rationale and study design of the Adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes (DILT1D): a non-randomised, open label, adaptive dose finding trial. BMJ Open 2014: 4: e005559 doi:10.1136/bmjopen-2014-005559

KC Herold, SE Gitelman, SM Willi, PA Gottlieb, F Waldron-Lynch, L Devine, J Sherr, SM Rosenthal, S Adi, MY Jalaludin, AW Michels, J Dziura, JA Bluestone. Teplizumab treatment improves C-peptide respones in subjects with Type 1 diabetes after the new onset period. Diabetologia. 2012 Oct 21. [Epub ahead of print]. PMID: 23086558

F Waldron-Lynch, O. Henegariu, S. Deng, P. Preston-Hurlburt, J. Tooley, R. Flavell, K.C. Herold. Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients. Science Translational Medicine 2012, 4, 118ra12. PMID: 22277969

F Waldron-Lynch and Kevan C. Herold Immunomodulatory therapy to preserve pancreatic beta cell function in type 1 diabetes. Nature Reviews Drug Discovery 2011.10 439-452. PMID: 21629294

COVER Gut Reaction.

Shown is an immunohistochemical stain of a duodenum in a teplizumab-treated humanized mouse. Teplizumab is a monoclonal antibody to CD3 being tested in clinical trials for type 1 diabetes. Waldron-Lynch et al. show that human lymphocytes (brown) migrate to the small intestine when treated with teplizumab but not control Ig. These cells then produce the immunoregulatory cytokine interleukin-10 (IL-10), and intestinal homing is critical for the treatment effects of teplizumab. A similar population of IL-10-producing cells was also observed in type 1 diabetes patients treated with teplizumab. [CREDIT: F. WALDRON-LYNCH, YALE UNIVERSITY SCHOOL OF MEDICINE]

 

October 11th, 2016

We successfully employed a state-of-the-art dose-finding, open label, adaptive clinical trial design in 40 participants with Type 1 diabetes to determine the doses of aldesleukin needed to raise T-regulatory white blood cell (Tregs) frequencies by 10% and 20%. Increased Treg frequencies induced by aldesleukin were preceded by a peak of aldesleukin in the blood at 90 minutes that caused a transient dose-dependent decrease of Tregs and other cell subsets in the circulation. Following treatment with a dose of aldesleukin, Tregs had a decreased sensitivity to IL-2 that returned to baseline on day 3 after treatment.