Reprogramming tumor microenvironment with precise photothermal therapy by calreticulin nanobody-engineered probiotics

Area of Science:

• Oncology
• Immunotherapy
• Biotechnology

Background:

• Targeted cancer therapies offer improved efficacy and safety but have limited patient eligibility due to a lack of suitable targets.
• Calreticulin (CALR) translocation to the cell surface upon immunogenic cell death (ICD) presents a potential therapeutic target.

Purpose of the Study:

• To investigate the potential of targeting cell surface CALR for cancer therapy.
• To develop and evaluate a novel nanobody-engineered probiotic system for targeted photothermal therapy (PTT).

Main Methods:

• Engineered probiotic Escherichia coli Nissle 1917 (EcN) with a nanobody (Nb215) targeting human and mouse CALR.
• Combined Nb215-modified EcN with indocyanine green (ICG) for near-infrared-II (NIR-II) imaging-guided photothermal therapy (PTT).
• Assessed the impact of PTT on tumor microenvironment, including immune cell infiltration and synergistic effects with CD47-SIRPα blockade.

Main Results:

• Nb215-modified EcN successfully targeted CALR and facilitated NIR-II imaging-guided PTT.
• PTT with EcN-215/ICG enhanced the infiltration of T cells and macrophages into the tumor microenvironment.
• The combination therapy demonstrated synergistic antitumor activity when combined with CD47-SIRPα axis blockade.

Conclusions:

• This study provides proof of concept for CALR-targeted therapy using engineered probiotics and PTT.
• CALR-targeted therapies hold significant promise for treating various cancers due to the widespread induction of CALR translocation.
• This approach offers a potential new avenue for enhancing the efficacy of existing cancer treatments.