IMMUNOLOGY, INFLAMMATION, PATHOBIOLOGY
Dr. Witkowski’s translational research has focused on testing novel cellular therapies and approaches: optimizing them first in the laboratory, investigating their safety and effectiveness in clinical trials, then introducing them into the clinical practice.
There are three main cellular therapies under investigation in Dr. Witkowski’s research group:
- Pancreatic islet allotransplantation in patients with “brittle” form of type 1 diabetes or those who have already undergone organ transplantation.
- Pancreatic islet autotransplantation in patients with severe chronic pancreatitis and intractable pain.
- Novel T regulatory cell therapy for induction of immunologic tolerance in transplant recipients and patients with autoimmune disease like type 1 diabetes, Crohn’s disease, rheumatoid arthritis, and multiple sclerosis.
Pancreatic islet allotransplantation has been developed as a minimally invasive therapy and alternative to whole pancreas transplantation. Pancreatic islets are isolated by Dr. Witkowski’s team from a cadaveric pancreas in The University of Chicago cGMP facility, a special lab designed for processing cells for clinical therapy. Islets are cultured in an incubator and once the patient is ready, infused via a portal vein into the patient’s liver under local anesthesia. This procedure takes up to one hour. After the procedure, the transplanted islets help diabetic patients restore proper glucose control, prevent life-threating severe hypoglycemic episodes and ultimately remove the need for insulin supplementation.
Currently, Dr. Witkowski is seeking additional research funding to continue optimization and efficiency of the procedure: protect patients from diabetes for longer periods of time, limit the need for immunosuppressive medication, limit side effects and reduce the necessary number of islets and number of transplants.
Pancreatic islet autotransplantation may benefit patients with chronic pancreatitis suffering from severe abdominal pain despite optimal medical and interventional treatment. These patients often have genetic mutations or a hereditary form of the disease, which progresses despite medical therapy. Patients with this level of pain eventually require long-term narcotic use, still with limited relief. Dr. Witkowski’s clinical team performs a total pancreatectomy (excision of the entire pancreas) as a “last resort” therapy, as total pancreatectomy causes an immediate onset of diabetes as the pancreas is the only source of insulin the human body. In order to improve glucose control after the surgery and prevent and/or control diabetes, Dr. Witkowski offers these patients islet autotransplantation. Islets are retrieved from from the patient’s own excised pancreas and then infused back into that same patient’s liver, where they engraft and control the patient’s blood glucose. The goal of this research is to improve the results of the infusion procedure, so more patients remain off insulin after the surgery.
Novel T regulatory cell therapy: The ultimate goal of the research in the field of the transplantation is to develop immunological tolerance to the transplanted organ or cells, without use of toxic anti-rejection medications. Dr. Witkowski has spent the last several years developing a novel cell therapy, which would ultimately replace immunosuppression. T-regulatory cells (Tregs) are known to have immunomodulatory properties and can prevent immunologic rejection or control autoimmune disease. In order to utilize Tregs in the clinical setting, Dr. Witkowski developed and optimized a Tregs ex vivo expansion protocol and conducted full-scale clinical grade Tregs expansion in the specialty cGMP facility at The University of Chicago. Dr. Witkowski’s subsequent goal is to conduct a phase 1/2 clinical study testing safety and efficacy of the approach in the context of liver or islet transplantation.