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Tumor Immunotherapy

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.

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Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology

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Anti-PD1-IL18 immunoconjugate promotes effector T cell-mediated antitumor immunity.

Nicole Oelgarth¹, Kea Martin², Fabian Junker²

¹Department of Biomedicine, University Hospital Basel, Basel, Switzerland.

Journal for Immunotherapy of Cancer

|July 14, 2026

Summary

This study introduces aPD1-IL18_mut, a novel immunoconjugate combining programmed cell death protein 1 (PD-1) blockade with interleukin-18 (IL-18) activation. It effectively targets tumor-reactive T cells, showing promise for overcoming resistance to cancer immunotherapies.

Keywords:

Antibody Cytokine Immune Checkpoint Inhibitor Immunotherapy

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Area of Science:

Immunology
Oncology
Biotechnology

Background:

Immune checkpoint inhibitors (ICIs) show limited efficacy in a significant patient subset due to resistance.
Immunocytokines offer a strategy to enhance antitumor immunity by delivering cytokines to the tumor microenvironment.
The novel immunoconjugate aPD1-IL18_mut combines PD-1 blockade with localized IL-18 immune activation.

Purpose of the Study:

To characterize the mechanism of action of aPD1-IL18_mut.
To evaluate its efficacy in preclinical models of cancer.
To assess its translational potential in human cancer samples.

Main Methods:

Chemical conjugation of anti-PD-1 antibody Lipustobart with an engineered IL-18 variant.
In vivo studies using human PD-1 transgenic mouse models (MC38 and YUMM1.7 tumors).
In vitro assays on human tumor samples and analysis of single-cell RNA sequencing datasets.

Main Results:

aPD1-IL18_mut enhanced IL-18 activity, preserving IFN-γ secretion.
It induced CD8+ T cell-mediated tumor control in MC38 tumors.
In anti-PD-1-resistant YUMM1.7 tumors, it activated CD4+ T cells, and in human samples, it enhanced tumor cell killing.
Analogous PD-1+IL-18Rɑ+ T-cell subsets were identified in human solid tumors.

Conclusions:

aPD1-IL18_mut activates tumor-reactive T cells (CD8+ and CD4+) and promotes IFN-γ-driven inflammation.
The immunoconjugate demonstrates efficacy across different tumor immune contexts.
Findings support the therapeutic potential of PD-1-targeted IL-18 therapy in human cancers.