Periodic Reporting for period 3 - Tumor microbiome (The tumor microbial communities: Characterization, effects and translational opportunities)
Período documentado: 2022-05-01 hasta 2023-10-31
In the current project, we suggested to greatly increase the characterization of the tumor microbiome, study its effects on tumor biology and capitalize on the findings to introduce novel treatment modalities. We hypothesize that bacteria in tumors have a yet unknown influence of many aspects of tumor biology and that better characterization of these effects would thus lead to completely new treatment options.
We have done a few screens looking for the effect of bacteria on response to anti-cancer drugs and decided to follow an interesting finding in which bacteria that are present in lung cancer can reduce the sensitivity of lung cancer cells to commonly used anti-cancer treatment. We are now working on dissecting the molecular mechanism by which the bacteria mediate this effect.
We have also been using bacteria as a novel anti-cancer drug. We found that some bacteria home preferentially to tumors upon their intravenous (IV) injection. We thus use attenuated bacteria that we genetically engineer to deliver payloads to the tumor. We show that the presence of the bacteria in the tumors and the specific payloads that we add to them can activate the immune response and lead to tumor retraction in multiple mice cancer models.
Most of the tumors that we studied thus far were obtained pre-treatment. To study the effect of treatments on the microbial community in tumors we are now studying cohorts from breast cancer patients in which the tumors were samples both pre and post treatment. We were able to identify bacteria that are highly enriched after therapy and are currently validating these results is additional cohorts as well as trying to understand why specific bacteria are enriched post treatment and the clinical importance of this observation.
We have previously demonstrated that specific bacteria can be found in human pancreatic tumors and can degrade the anti-cancer drug gemcitabine and thus confer drug resistance. Now, using advanced technology, which allows us to grow human tumors in the lab, we are exploring how addition to antibiotics can synergize with gemcitabine. These experiments, if successful, would hopefully lead to clinical trials in pancreatic cancer patients.
We are also putting a lot of effort is engineering bacteria that we deliver to tumor to express more and better payloads, in order to optimize their effects. We are testing the effects of our bacteria on mice tumor models and explore not only the effect on tumor size but also the effect of the mice systemic immune profile and on the tumor immune landscape. Here as well, we hope to be able to translate our findings into clinical trial in human patients.