How Do Allogeneic Islet Cells Work?

Allogeneic islet cells are a cellular therapy used to treat patients with type I diabetes mellitus. Type I diabetes is a chronic autoimmune disease in which the immune system attacks the pancreas. People with this condition produce little or no insulin, a hormone that is essential for glucose metabolism.

Type I diabetes is a condition that causes the blood sugar to become dangerously high (hyperglycemia) because the immune system mistakenly destroys the beta cells in the pancreas that produce insulin. Insulin is a hormone that moves blood sugar into tissue cells for conversion into energy, induces the liver to store excess glucose as glycogen, and helps maintain normal blood sugar levels.

The beta cells in the islets of Langerhans in the pancreas secrete insulin when the blood sugar levels go up, and stop the secretion when glucose levels become normal. In addition to insulin, the pancreatic islets produce various hormones such as glucagon, ghrelin, pancreatic peptide, and somatostatin, which regulate glucose and energy metabolism, appetite, digestion, and growth.

Allogeneic islet cells are pancreatic islet cells collected from deceased donor pancreas, and suspended in a solution of sodium chloride, dextrose, minerals, vitamins, and other compounds. The islet cells are slowly infused into a patient’s portal vein that carries blood from the gastrointestinal tract to the liver.

Within 2 weeks of infusion, the islets lodge themselves in the recipient’s liver blood vessels, and start secreting insulin into the bloodstream. Natural secretion of insulin within the body helps better maintain optimum sugar levels than with insulin administration which can sometimes lead to dangerously low blood sugar (hypoglycemia).

Conventional treatment requires daily insulin injections and glucose monitoring. Patients in clinical trials have remained insulin-independent for periods ranging from less than a year to longer than 5 years, but some have continued to require insulin. Typically, patients are administered up to 3 infusions of allogeneic islet cells.

Currently, the first-in-class and only allogeneic islet cell therapy approved by the FDA is donislecel (Lantidra), which is collected from deceased donors. It is administered in conjunction with therapy for immunosuppression. Trials have been conducted with islet cells collected from living donors, however, these therapies are still investigational.

Allogeneic islet cells are formulated as a cellular suspension, which is administered as infusions into the hepatic portal vein. The therapy is approved by the FDA to treat adults with type I diabetes mellitus, who are unable to approach target Hb1Ac because of recurrent hypoglycemia episodes despite intensive treatment. It is administered along with immunosuppressive medications.

Common side effects of allogeneic islet cells include the following:

• Immunosuppression effects including:
  • Infections
  • Malignancy
• Infusion procedure effects including:
  • Liver laceration
  • Liver hematoma
  • Liver hemorrhage
  • Intraabdominal bleeding
  • Increase in portal blood pressure (portal hypertension)
  • Contusion
  • Nausea
  • Vomiting
  • Diarrhea
  • Abdominal pain
  • Dry mouth
  • Mouth ulceration
  • Oral inflammation (stomatitis)
  • Fatigue
  • Weakness (asthenia)
  • Anemia
  • Low white cell count (leukopenia)
  • Headache
  • Upper respiratory tract infection
  • Urinary tract infection
  • Electrolyte imbalances in the blood including:
  • Low sodium (hyponatremia)
  • High potassium (hyperkalemia)
  • Low calcium (hypocalcemia)
  • Low magnesium (hypomagnesemia)
  • Decrease in blood carbonate
  • Increase in liver enzymes (transaminases)
  • Increase in liver enzyme aspartate aminotransferase
  • Fatty liver (hepatic steatosis)
  • High bilirubin levels in blood (hyperbilirubinemia)
  • Low albumin levels in blood (albuminemia)
  • High blood cholesterol (hypercholesterolemia)
  • Increase in low-density lipoprotein (LDL)
  • Muscle pain (myalgia)
  • Muscle spasms
  • Joint pain (arthralgia)
  • Musculoskeletal pain
  • Pain in extremity
  • Chills
  • Feeling cold
  • Thirst
  • Swelling of extremities (peripheral edema)
  • Sinus inflammation (sinusitis)
  • Decrease in hemoglobin
  • Ringing in the ears (tinnitus)
  • Ear pain
  • Eye pain
  • Blurred vision
  • Thyroid tumor (neoplasm)
  • Decreased appetite
  • Loss of appetite (anorexia)
  • Appetite disorder
  • Eating disorder (bulimia)
  • Abnormal weight loss
  • High blood pressure (hypertension)
  • Palpitations
  • Pneumonia
  • Herpes zoster
  • Irregular menstruation
  • Anxiety
  • Depression
  • Lack of pleasure (anhedonia)
  • Disturbance in attention
  • Insomnia
  • Nervousness
  • Reduced touch sensation (hypoesthesia)
  • Dizziness
  • Tremor
  • Overactive (hypertonic) bladder
  • Blood in urine (hematuria)
  • Frequent daytime urination (pollakiuria)
  • Frequent urination in the night (nocturia)
  • Urinary incontinence
  • Hoarse voice (dysphonia)
  • Cough
  • Shortness of breath (dyspnea)
  • Nasal congestion
  • Sinus disorder
  • Mouth and throat (oropharyngeal) pain
  • Dry skin
  • Acne
  • Rash
  • Itching (pruritus)
  • Nail separation from nail bed (onychoclasis)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of allogeneic islet cells include:

• donislecel
• Lantidra