Development of a Novel Immunotherapy Leveraging the Mechanism of Dead Cell Clearance

A research group at the Osaka International Cancer Center (located in Chuo Ward, Osaka City; President: Shigeaki Matsuura), part of the Osaka Prefectural Hospital Organization under the Independent Administrative Institution Law, has successfully developed a novel artificial protein, 'Strap (PStRAP)', designed to enhance the body's immune response and thereby increase the effectiveness of anticancer drugs. This research was published online on May 26, 2026 (Eastern Standard Time, USA) in Molecular Therapy, the official journal of the American Society of Gene & Cell Therapy (ASGCT), with print publication scheduled for the August 2026 issue.

This research is expected to directly contribute to the development of new cancer therapies.

About the Artificial Protein 'Strap (PStRAP)'

The research team, led by Yu Mizote, Principal Researcher in the Cancer Immunotherapy Development Unit at the Advanced Exploratory Research Division of the Next-Generation Cancer Medical Development Research Center, and Hideaki Tahara, Director of the Clinical Research Center, developed the new artificial protein 'Strap (PStRAP)' through joint research with Nitto Denko Corporation. This protein enhances the body's immune response to increase the efficacy of chemotherapy.

The human body has an immune system that eliminates foreign invaders. When pathogens such as bacteria or viruses enter the body, they are attacked and destroyed. In contrast, when our own cells die, they become cellular debris that must be removed to prevent accumulation. This removal process differs from pathogen elimination, as it occurs 'silently'—without triggering an immune response or attacking the dying cells. It has become clear that cancer cells exploit this mechanism to evade immune detection and survive. Therefore, the research group artificially developed a protein called 'Strap' that converts this normally immune-suppressing 'silent clearance mechanism' into one that enhances immunity. When administered to mice with cancer, 'Strap' strengthened the immune response against cancer cells and enhanced the therapeutic effect of anticancer drugs.

[Key Points of the Study]

- Using the novel artificial protein 'Strap', researchers were able to harness phosphatidylserine—the 'marker' exposed on cells during in vivo processing—to induce immune responses against cancer

- 'Strap' can be applied not only as a direct protein formulation but also in the form of 'mRNA medicine', a recently emerging modality, demonstrating its potential for cancer therapy

- Clinical trials based on these findings are expected to establish 'Strap' as a groundbreaking immunotherapy unlike any seen before

[Research Background]

In the human body, aged or damaged cells undergo a form of programmed cell death called 'apoptosis (Note 1)', and are promptly engulfed and removed by 'clean-up' cells (phagocytosis (Note 2)). At this time, a 'marker' called 'phosphatidylserine (Note 3)' appears on the surface of dying cells, signaling 'eat me' to the clean-up cells.

Normally, this mechanism ensures that dead cells from our own body are processed quietly and without triggering an immune response, minimizing impact on surrounding tissues. However, when cancer cells die due to treatment, they also expose phosphatidylserine and are 'quietly' processed, which is believed to prevent a strong immune response against the cancer.

Therefore, the research group hypothesized that 'if this clearance pathway could be switched to one that enhances immunity, dead cancer cells could be used to induce a powerful immune response against the tumor'.

[Research Content]

The research group artificially designed a new protein, 'Strap (PStRAP) (Note 7)', by linking a portion of 'MFG-E8 (Note 4)', a protein that binds to the 'marker' phosphatidylserine on dead cells, with 'RAP (Note 6)', a protein that binds to 'CD91 (Note 5)', a receptor that enhances immune responses.

'Strap' acts as a bridge between dead cells exposing phosphatidylserine and immune cells expressing CD91, thereby converting the normal immune-suppressing clearance pathway into one that enhances immunity.

Studies using mice revealed the following:

- In the presence of 'Strap', the process from phagocytosis of dead cells to immune activation occurred smoothly, enhancing the activity of killer T cells (Note 8)—immune cells that attack cancer cells—and triggering a strong immune response against live cancer cells

- Systemic administration of 'Strap' using mRNA-LNP (Note 9) technology also demonstrated similar anticancer drug-enhancing effects

Enhancement of Anticancer Drug Efficacy by PStRAP

[Future Outlook]

The 'Strap' developed in this study has shown potential as a new cancer treatment by enhancing immune responses against various types of cancer.

Moving forward, the team plans to conduct clinical trials to evaluate its use in actual cancer patients and to study its combination with existing immunotherapies to further enhance treatment efficacy.

From left: Yu Mizote, Principal Researcher, Cancer Immunotherapy Development Unit, Advanced Exploratory Research Division, Next-Generation Cancer Medical Development Research Center; Hideaki Tahara, Director, Clinical Research Center

◇ Paper Title and Authors:

〇 Journal Name:

Molecular Therapy DOI: https://doi.org/10.1016/j.ymthe.2026.05.013

〇 Paper Title:

“Restricting efferocytosis pathway to CD91 via phosphatidylserine-targeting chimeric protein augments antitumor immune responses”

〇 Authors:

Yu Mizote1,2,†,*, Hiroki Nishita3,4,†, Kazuki Hashiba4, Chisa Okuma4, Sachiko Akane4, Kenjiro Minomi4, and Hideaki Tahara1,3,5

†: Co-first authors, *: Corresponding author

〇 Affiliations:

1. Department of Cancer Drug Discovery, Institute for Cancer Research, Osaka International Cancer Institute

2. Department of Cancer Immunotherapy Development, Institute for Cancer Research, Osaka International Cancer Institute

3. Nitto Nucleic Acid Drug Joint Research Department, Institute for Cancer Research, Osaka International Cancer Institute

4. Nucleic Acid Medicine Development Division, Nitto Denko Corporation

5. Clinical Research Center, Osaka International Cancer Institute

* The 'Institute for Cancer Research' will be renamed the 'Next-Generation Cancer Medical Development Research Center' starting in fiscal year 2026.

◇ Term Explanations:

(Note 1) Apoptosis:

Physiological cell death initiated autonomously by the cell—essentially 'cell suicide'.

A mechanism to safely eliminate unnecessary or damaged cells.

(Note 2) Phagocytosis:

The process by which 'clean-up' cells engulf (eat) and degrade cells or foreign substances.

Carried out by immune cells such as macrophages and dendritic cells.

(Note 3) Phosphatidylserine (PS):

A type of phospholipid that constitutes the cell membrane.

In living cells, PS faces the inner side of the membrane, but during cell death