How Does Interleukin-2 (IL-2)-Diphtheria Toxin Fusion Protein Work?

Interleukin-2 (IL-2)-diphtheria toxin fusion protein is a biological product used for the treatment of cutaneous T-cell lymphoma (CTCL) in adults. IL-2-diphtheria toxin fusion protein is a kind of treatment that is designed to kill cancer cells in cutaneous T-cell lymphoma by carrying and releasing the diphtheria toxin inside the tumor cells.

Cutaneous T-cell lymphomas are a group of rare cancers that start in the T-lymphocytes, also known as T-cells, an integral part of the immune system. CTCL affects the skin, but it is not a skin cancer. It is a type of lymphoma in which T-cells within the skin become cancerous, cause inflammations and rashes, and damage the skin.

The skin contains a large number of T-cells which help fight infections. CTCL occurs when these T-cells turn abnormal and grow out of control. Initially it only affects the skin, but can spread to other organs such as lymph nodes, liver and spleen, in advanced stages. CTCL is classified as a type of non-Hodgkin lymphoma (NHL).

Interleukin-2 is a protein produced by activated T-cells, and is a growth factor that promotes the growth of T-cells. The activated T-cells in the skin in cutaneous T-cell lymphomas produce this protein which aids the cancerous growth of T-cells. Interleukin-2 (IL-2)-diphtheria toxin fusion protein binds to IL-2 receptors on the tumor cells and kills them.

Interleukin-2 (IL-2)-diphtheria toxin fusion protein is produced using DNA recombinant technology and contains human IL-2 and diphtheria toxin fragments. The IL-2 helps the drug bind to T-cells that express IL-2 receptors, and once the molecule enters the cell, the diphtheria toxin separates and inhibits protein synthesis, which leads to cell death.

Currently, the only approved interleukin-2 (IL-2)-diphtheria toxin fusion protein therapy is denileukin diftitiox. It was originally approved by the FDA to treat CTCL, under the brand name of Ontak in 1999. Ontak was withdrawn in 2014, and the treatment has now been approved in August 2024 under the brand name of Lymphir.

Interleukin-2 (IL-2)-diphtheria toxin fusion protein is administered as an intravenous infusion over 60 minutes, on days 1 through 5 of 21-day treatment cycles. The patient is also administered pre-medications to reduce the risk of infusion reactions, particularly during the first 3 cycles.

Interleukin-2 (IL-2)-diphtheria toxin fusion protein is approved by the FDA for adult patients with relapsed or refractory Stage I-III cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.

Some of the common side effects of Interleukin-2 (IL-2)-diphtheria toxin fusion protein include the following:

• Nausea
• Diarrhea
• Vomiting
• Constipation
• Liver toxicity
• Increase in bilirubin
• Increase in liver enzymes:
• Alanine aminotransferase (ALT)
• Aspartate aminotransferase (AST)
• Alkaline phosphatase
• Decrease in lymphocytes
• Decrease in albumin
• Decrease in hemoglobin
• Increase in creatine phosphokinase
• Infusion-related reactions including:
• Fatigue
• Swelling from fluid retention (edema)
• Chills
• Fever (pyrexia)
• Musculoskeletal pain
• Joint pain (arthralgia)
• Nausea
• Vomiting
• Headache
• Dizziness
• Changes in mental state
• Rash
• Itching (pruritus)
• Capillary leak syndrome
• Decreased appetite
• Blurred vision
• Changes in color vision
• Changes in visual acuity
• Weight increase
• Skin infections
• Kidney insufficiency
• Insomnia
• Thyroid disorders including:
• Hyperthyroidism
• Thyroiditis
• Thyrotoxicosis
• Hypothyroidism
• Development of anti-denileukin diftitox antibodies
• Development of anti-IL-2 antibodies
• Sepsis
• Peripheral nerve disease (neuropathy)

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 Interleukin-2 (IL-2)-diphtheria toxin fusion protein include:

• denileukin diftitox
• denileukin diftitox-cxdl
• Lymphir