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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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Related Experiment Video

Updated: Jan 7, 2026

Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses

Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses

Published on: May 6, 2019

Targeting highly attenuated IL-18 to PD-1 for enhanced anti-tumor activity.

Xueyuan Zhou¹, Felix Klaus Geyer², Jeffrey Takimoto¹

¹Drug Discovery and Development, Fuse Biotherapeutics, Woburn, MA, United States.

Frontiers in Immunology

|January 5, 2026

Summary

This study developed a novel cancer therapy by fusing an attenuated interleukin-18 (IL-18) to a PD-1 inhibitor. This approach enhances anti-tumor immunity by activating T cells and blocking immune checkpoints simultaneously.

Keywords:

IL-18 PD-1 checkpoint inhibitor cytokine immunocytokine

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Last Updated: Jan 7, 2026

Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses

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Published on: May 6, 2019

Evaluation of the In vivo Antitumor Activity of Polyanhydride IL-1α Nanoparticles

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Published on: June 28, 2021

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

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

Published on: May 2, 2025

Area of Science:

Immunology
Oncology
Biotechnology

Background:

Cancer immunotherapy using checkpoint inhibitors like anti-PD-1 has limitations in response rates.
Next-generation therapies aim to combine checkpoint blockade with cytokine potentiation for enhanced efficacy.
Balancing cytokine activity with checkpoint inhibition to manage toxicity is a significant challenge.

Purpose of the Study:

To investigate the efficacy of a novel fusion protein combining a highly attenuated interleukin-18 (IL-18) with an anti-PD-1 antibody.
To determine if this fusion protein can simultaneously inhibit PD-1 and activate PD-1+ T cells to overcome cancer immune evasion.
To assess the therapeutic potential and safety profile of this dual-action immunotherapy.

Main Methods:

Generation of a highly attenuated IL-18 variant resistant to IL-18 binding protein (IL-18BP).
Assessment of the variant's receptor binding and cis-signaling capabilities.
Evaluation of tumor growth inhibition in multiple preclinical cancer models.
Analysis of post-remission tumor resistance and tumor-infiltrating lymphocyte populations via flow cytometry.

Main Results:

The attenuated IL-18 fusion protein demonstrated resistance to IL-18BP inhibition and a significant reduction in activity (10,000-fold) while maintaining cis-signaling.
The fusion protein showed strong efficacy across various tumor models, inhibiting tumor growth effectively.
Treatment led to an increase in CD8+ progenitor-exhausted tumor-infiltrating lymphocytes (TILs) and a decrease in myeloid TILs.

Conclusions:

Targeting a highly attenuated IL-18 to PD-1 represents a novel strategy for cytokine-enhanced checkpoint inhibition.
This approach activates PD-1+ T cells via the cytokine receptor while simultaneously antagonizing PD-1, offering a dual mechanism of action.
The developed fusion protein shows promise as a next-generation cancer immunotherapy with potential for improved efficacy and manageable toxicity.