Back to Our Technologies

Engineering Bacteria To Enhance Cytokine Activity in Immunotherapy Response

Bacterial surface display used to deliver immune-activating cytokines for cancer therapy, enabling safe, efficient targeting of the tumor microenvironment (TME).

  • Therapeutics

Project Overview

  • Current cancer immunotherapies face significant hurdles, particularly in solid tumors, including lack of tumor-specific targets, poor tumor trafficking of the immune effector cells, and their dysfunction and exhaustion in the highly immune-suppressive tumor microenvironment (TME).
  • Engineered non-pathogenic bacteria have shown some promise in delivering therapeutic payloads to boost the efficacy of immunotherapy. However, these approaches have relied on secretion or self-lysis which limit the duration and extent of their efficacy.
  • Scientists at Dana-Farber have developed a method for safe, efficient, and preferential delivery of cytokines to the TME.
  • Dana-Farber is looking for licensing and collaboration opportunities to further develop this technology preclinically and into the clinic. 

Technology

Dana-Farber researchers pioneered the use of bacterial surface display technologies to deliver immune-activating cytokines for cancer immunotherapy. They demonstrated that expression of IL-15, IL-18, decoy-resistant IL-18 mutein (DR18) and IL-21 on the bacterial outer membrane enhances the cytokines’ ability to effectively induce potent immune responses through surface anchoring and clustering.

By using non-pathogenic facultative anaerobe bacteria isolated from native gut microbiota in humans, they achieved safe, efficient, and preferential delivery of cytokines to the TME. In vivo proof of concept was demonstrated with both murine and human cytokines in combination with CAR NK cells in relevant preclinical models of colorectal cancer, melanoma, and mesothelioma.

Further Details:

Benefits:

Among the many attempts to enhance current immunotherapies, bacterial surface display of immune-stimulatory cytokines emerges as a singularly creative approach poised to safely and effectively address several clinical challenges. This approach:

  • Enhances tumor trafficking and therapeutic efficacy of mesothelin-targeting CAR NK cells in murine models of mesothelioma.
  • Leads to preferential TME delivery and enhanced exposure and retention of key immune-activating cytokines.
  • Elicits robust CD8+ T cell and natural killer (NK) cell-dependent immune responses.
  • Demonstrates abscopal and recall responses, suggesting epitope spreading and induction of immunologic memory.

Team Members: Rizwan Romee, MD, Michal Sheffer, PhD, Shaobo Yang, PhD, Jiahe Li, PhD

Applications

This innovative approach offers a promising new avenue for cancer treatment, addressing the limitations of current therapies and providing a versatile platform for future developments in oncology.

  • Direct Tumor Treatment: Intratumoral administration to reduce tumor size and modulate the TME.
  • Combination Therapies: Used alongside CAR-NK or CAR-T cell therapies to enhance immune cell activation and tumor targeting.
  • Systemic Therapy: Intravenous administration for metastatic cancers, leveraging the abscopal effect.
  • Personalized Medicine: Tailoring bacterial strains and cytokine displays to individual patient tumor profiles for optimized treatment outcomes.

Opportunities

Dana-Farber is looking for licensing and collaboration opportunities to further develop this technology preclinically and into the clinic. 

Get in touch

Team Members