Edwin Manuel Lab

Research Lab Overview

Our laboratory is focused on novel strategies to enhance delivery and efficacy of anti-cancer therapy. The majority of our work utilizes microbial-based agents developed to serve specific functions, such as the depletion of extracellular components or modification of the suppressive immune repertoire found in tumors.

These novel agents are validated using pre-clinical models that faithfully recapitulate tumor architecture and immune suppression found in cancer patients. Currently, our research focuses on two main areas:

1. Targeting the extracellular matrix in fibrotic tumors to maximize anti-cancer drug delivery
2. Modifying the immune contexture to improve immunotherapeutic efficacy

Research Highlights

Targeting the extracellular matrix in fibrotic tumors to maximize therapeutic delivery

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the development of a fibrotic barrier, mostly composed of the extracellular matrix (ECM) components hyaluronan and collagen, that prevents efficient delivery of standard chemotherapy and other anti-cancer agents.

Using our tumor-colonizing Salmonella typhimurium platform, we have successfully developed two unique recombinant strains capable of degrading tumor-derived hyaluronan and collagen. Studies to determine changes in tumor growth when used alone or in combination with standard chemotherapy or immune checkpoint blockade are currently ongoing.

Modifying the tumor immune contexture to improve immunotherapeutic efficacy

The immune landscape present in lung tumors is dominated by suppressive immune subsets which include Tregs and pro-tumor myeloid-derived cells. We have developed several strains of attenuated Salmonella typhimurium to target immunosuppressive protein expression or to secrete specific cytokines/chemokines, which has the potential to dramatically change the immune contexture in tumors and generate a more conducive microenvironment for immunotherapeutic treatment.

We are currently determining if administration of our engineered strains acts synergistically with checkpoint blockade in pre-clinical models of lung cancer.