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NHS-IL12, a Tumor-Targeting Immunocytokine
John W Greiner1, Y Maurice Morillon1, Jeffrey Schlom1
1Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Immunotargets and Therapy
|June 3, 2021
Summary
NHS-IL12, a novel immunocytokine, effectively targets tumors and enhances anti-tumor immunity by boosting immune cells and reducing suppressive myeloid cells. This leads to significant tumor growth reduction, especially when combined with other therapies.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Interleukin-12 (IL-12) is a cytokine crucial for immune responses against tumors.
- Delivering IL-12 to the tumor microenvironment (TME) effectively is challenging.
- Novel strategies are needed to enhance IL-12's anti-tumor capabilities and delivery.
Purpose of the Study:
- To evaluate NHS-IL12, a novel immunocytokine targeting DNA/histone complexes in tumors.
- To compare the efficacy of NHS-IL12 with recombinant IL-12 (rIL-12) in preclinical models.
- To assess NHS-IL12's impact on immune cell populations and tumor growth within the TME.
Main Methods:
- Fusion of IL-12 to a DNA/histone-binding antibody (NHS76) to create NHS-IL12.
- Preclinical studies in murine models to assess tumor targeting, pharmacokinetics, and anti-tumor activity.
- Analysis of immune cell populations (immune cells, antigen-presenting cells, myeloid-derived suppressor cells, macrophages) in the TME.
- Combination therapy studies with chemotherapy and immunotherapy.
Main Results:
- NHS-IL12 demonstrated enhanced tumor targeting and a longer plasma half-life compared to rIL-12.
- NHS-IL12 significantly improved immune cell proliferation and activation, leading to a stronger primary immune response.
- Administration of NHS-IL12 reduced immunosuppressive myeloid cells in the TME and substantially inhibited tumor growth in a murine bladder cancer model.
- Preclinical studies indicated improved anti-tumor efficacy when NHS-IL12 was combined with other therapeutic approaches.
Conclusions:
- NHS-IL12 is a promising immunocytokine with superior tumor-targeting and immune-modulating properties compared to rIL-12.
- NHS-IL12 effectively reshapes the TME by increasing anti-tumor immunity and decreasing immunosuppressive cells.
- NHS-IL12 holds potential as a therapeutic agent for cancer treatment, particularly in combination strategies.
