Switchable immune modulator for tumor-specific activation of anticancer immunity

Area of Science:

• Biotechnology
• Immunology
• Chemical Biology

Background:

• Immune stimulatory antibodies and cytokines show promise for cancer treatment.
• Systemic toxicity limits the clinical use of potent immune modulators (IMs).

Purpose of the Study:

• To develop a chemical strategy to reduce systemic toxicity of immune modulators.
• To enhance the therapeutic window of IMs by targeting them to the tumor microenvironment.

Main Methods:

• Developed "switchable" immune modulators (Sw-IMs) using biocompatible polymers and tumor-specific linkers.
• Sw-IMs are masked in circulation and activated by tumor microenvironment stimuli (e.g., low pH, high reducing potential).
• Tested Sw-IMs based on anti-4-1BB antibody and IL-15 cytokine in preclinical models.

Main Results:

• Sw-IMs demonstrated selective reactivation within the tumor microenvironment.
• Sw-IMs achieved antitumor efficacy comparable to parental IMs.
• Markedly reduced systemic toxicities were observed with Sw-IMs compared to conventional IMs.

Conclusions:

• Sw-IMs offer a modular and versatile platform for improving the safety and efficacy of immune-based cancer therapies.
• This approach enhances the therapeutic index of potent immune modulators for both monotherapy and combination treatments.