It is also being investigated as a possible countermeasure for people exposed to a high-level radiation dose, specifically to counter what is known as hematopoietic syndrome of acute radiation syndrome (HSARS). This condition, also referred to as radiation sickness, results in reduced numbers of red and white blood cells, and platelets.
How NM-IL-12 works
Interleukin-12 (IL-12) is a cytokine, or cell signaling protein, that enhances the activity of natural killer (NK) cells and T-cells, which are immune system cells responsible for combating infections or threats against the body. It creates a connection between innate and adaptive immunity, and has demonstrated clinical effects in melanoma, T-cell lymphoma, and non-Hodgkin’s lymphoma (NHL) as a promising therapeutic agent. However, the high doses and repeat-dosing regimens used in oncology trials generally resulted in excessive side effects accompanied by more modest clinical response and benefit. As these early clinical trials did not meet expectations, further development of IL-12 was not pursued.
IL-12 potentially prevents or inhibits the development of cancer by binding to and activating its cell-surface receptor, stimulating the production of interferon-gamma (IFN), which is another cytokine that coordinates natural mechanisms of an anticancer defense.
This cytokine is also capable of stimulating hematopoiesis (the production of red and white blood cells, as well as platelets) due to a direct action on the stem cells in the bone marrow, thereby promoting the proliferation and/or differentiation of hematopoietic progenitor cells.
NM-IL-12 is a recombinant form of the endogenous IL-12; it acts like IL-12 but can be administrated at low doses and combined with standard of care for a range of cancers: radiotherapy, chemotherapy, or immunotherapy. NM-IL-12 is expected to increase the anti-tumor effects of each of these treatments.
NM-IL-12 in clinical trials
The safety, tolerability, pharmacokinetics (how the body affects a drug), and pharmacodynamics (how a drug affects the body) of a single dose of recombinant human interleukin-12, called rHuIL-12, was tested in healthy volunteers in a placebo-controlled and double-blinded Phase 1 study (NCT01742221). Results showed the drug to be safe, well-tolerated, and found it stimulated the innate immune response “without undue toxicity.”
In Phase 1 and Phase 2 clinical studies, recombinant IL-12 monotherapy was shown to be effective in CTCL, inducing tumor regression and achieving complete responses in some cases.
Studies in mouse disease models also showed that recombinant IL-12, used in combination with other anticancer therapies, may protect the body against tumors, inhibiting their growth and inducing cytotoxicity against B-cell lymphomas.
An open-label Phase 2 clinical trial (NCT02542124) is now enrolling about 10 patients with CTCL to evaluate NM-IL-12 as immunotherapy when combined with low-dose radiation therapy. The study is recruiting at sites in the U.S.
The safety, tolerability, and efficacy of NM-IL-12 will also be investigated in about 12 people with advanced (relapsed or refractory) DLBCL in an open-label Phase 2 clinical trial (NCT02544724). This study is not yet open for patient recruitment.
The most common side effects related to NM-IL-12 were headache, dizziness, and chills.
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