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ASH 2025 | LIME: a first-in-class of live bacterial immune engagers for cancer immunotherapy
In this interview, Anna Clara Bader, MD, Dana Farber Cancer Institute, Boston, MA, and Julius Maximilian University of Würzburg, Würzburg, Germany, briefly discusses the development of Live Immune Modulating Engagers (LIME), a novel platform for targeted cancer immunotherapy that uses non-pathogenic E. coli to display bispecific single-chain variable fragments (scFvs) targeting both tumor-associated antigens (TAAs) and immune cell (T or NK) receptors. This approach is being developed to drive tumor-specific killing while minimizing systemic toxicity. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
LIME is a live bacterial immune engager. We de facto express both an anti-tumor binding region as well as an anti-factor cell binding region on one E. coli. So you then have an entire immune engager on an E. coli. And we do that because E. coli are gram-negative bacteria and like some other gram-negative bacteria, in facultative anaerobic regions, such as the microenvironment of tumors, and therefore, if you engineer the bacteria, they then directly go to the tumor microenvironment, taking the therapy you delivered on top of them with them...
LIME is a live bacterial immune engager. We de facto express both an anti-tumor binding region as well as an anti-factor cell binding region on one E. coli. So you then have an entire immune engager on an E. coli. And we do that because E. coli are gram-negative bacteria and like some other gram-negative bacteria, in facultative anaerobic regions, such as the microenvironment of tumors, and therefore, if you engineer the bacteria, they then directly go to the tumor microenvironment, taking the therapy you delivered on top of them with them. And we use a surface display platform to then deliver the immune engager to the tumor microenvironment.
We showed in vitro killing efficacy binding as well as proliferation and also in vivo had immune-competent mouse models as well as humanized mouse models and SCID models and the next step would then be non-primate models to try to get it into the clinic and into clinical testing, but for safety reasons we first have to do a non-primate model, even though we didn’t see any signs of CRS right now but just to take it to the next step.
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