Periodic Reporting for period 4 - BARCODE DIAGNOSTICS (Next-Generation Personalized Diagnostic Nanotechnologies for Predicting Response to Cancer Medicine)
Berichtszeitraum: 2020-10-01 bis 2022-03-31
This ERC-StG research program aims to integrate nanotechnology and personalized cancer medicine. More specifically, to develop nanoparticles that act as localized sensors for detecting which medication regimen is best for treating metastatic cancer in a personalized manner. Achieving this goal requires fundamental nanotechnological discoveries and developments, for example – elucidating the requirements and ability of nanoparticles to target metastatic breast cancer.
Barcode Diagnostics is addressing one of the pressing issues in cancer – determining the best medicine for treating each cancer patient. Our first focus is metastatic breast cancer. Despite being the most prevalent cancer among women, nearly one-third of patients receive medicine that does affect their primary tumor. In metastatic patients, this becomes even more challenging, where more than half of the patients do not respond to treatment.
Our overall objective was to develop a nanotechnological platform that will perform a rapid diagnostic assay to determine which medicine is best for a specific patient. In parallel, we worked on developing new nanoparticles that can be used as a drug production system, opening some new cancer treatment strategies.
To achieve this goal, we developed nanoparticles that upon intravenous injection target the cancerous tissue and perform a diagnostic assay on the malignant cells inside the patient’s body. More specifically, a cocktail of nanoparticles, each loaded with a miniscule dose of a different drug are injected intravenously. The particles were engineered to target the tumor and metastasis. Then, the activity of the different medicines, loaded into each of the particles on the cancer cells, is detected using a newly developed molecular barcoding system.
The developed technology was the basis for the establishment of Barcode company. That provides the medical and scientific communities with better understanding regarding the personalized activity of drugs in patients, and following clinical experiments will become a new tool for diagnosing and treating cancer.
The outcomes of the project start with the contribution to Science reflected by 18 scientific papers published in leading peer-reviewed journals, and multiple prizes received by Prof. Avi Schroeder and the students, among them prestige Krill Award, granted by the Wolf Foundation. The project also contributes to community through public lectures, organized visits to the lab and online interviews about the conducted research.
This ERC project made a significant economic contribution, which can be distinguished by the fact that multiple startup spinoff companies were established during project life focusing on DNA, RNA, and protein-based nano-therapies, employing nearly 100 people full time.
Barcode Diagnostics is addressing one of the pressing issues in cancer – determining the best medicine for treating each cancer patient. Our first focus is metastatic breast cancer. Despite being the most prevalent cancer among women, nearly one-third of patients receive medicine that does affect their primary tumor. In metastatic patients, this becomes even more challenging, where more than half of the patients do not respond to treatment.
Our overall objective was to develop a nanotechnological platform that will perform a rapid diagnostic assay to determine which medicine is best for a specific patient. In parallel, we worked on developing new nanoparticles that can be used as a drug production system, opening some new cancer treatment strategies.
To achieve this goal, we developed nanoparticles that upon intravenous injection target the cancerous tissue and perform a diagnostic assay on the malignant cells inside the patient’s body. More specifically, a cocktail of nanoparticles, each loaded with a miniscule dose of a different drug are injected intravenously. The particles were engineered to target the tumor and metastasis. Then, the activity of the different medicines, loaded into each of the particles on the cancer cells, is detected using a newly developed molecular barcoding system.
The developed technology was the basis for the establishment of Barcode company. That provides the medical and scientific communities with better understanding regarding the personalized activity of drugs in patients, and following clinical experiments will become a new tool for diagnosing and treating cancer.
The outcomes of the project start with the contribution to Science reflected by 18 scientific papers published in leading peer-reviewed journals, and multiple prizes received by Prof. Avi Schroeder and the students, among them prestige Krill Award, granted by the Wolf Foundation. The project also contributes to community through public lectures, organized visits to the lab and online interviews about the conducted research.
This ERC project made a significant economic contribution, which can be distinguished by the fact that multiple startup spinoff companies were established during project life focusing on DNA, RNA, and protein-based nano-therapies, employing nearly 100 people full time.
Our studies commenced with the development of the Barcoded Nanoparticles - 100-nanometer liposomes, loaded with an anti-cancer agent and a molecular barcode that allows tracking the particle in the body. In our Nature Communications paper (Yaari. et al, 2016), we tested this approach in a Triple Negative Breast Cancer (TNBC) model and showed the barcoded nanoparticle system predicts the activity of the different drugs inside the tumor. Specifically, we were able to distinguish between active and inactive drugs.
Using targeted nanotechnologies allowed rapid analysis of drug activity (96 hours) and ensured the system's safety by using minuscule doses (~1/1000 the therapeutic dose). During the project, we explored how different cell types in the tumor microenvironment and metastasis respond to medication and correlated this to genomic data.
During the ERC-StG research program period, we demonstrated for the first time that artificial particles that mimic natural cells, coined – synthetic cells (SC), containing the molecular machinery necessary for carrying out transcription and translation, were used to synthesize anti-cancer RNA biologics inside tumors (Krinsky. et al, 2016 and Krinsky. et al, 2018) and communicate with living cells through light (optogenetic) signals. These findings were recently published in Nature Communications (Adir. et al, 2022).
We also showed the importance of gender (patient’s sex) in nanomedicine design and the effect of nanoparticles accumulation in the female reproductive system on cancer treatment and fertility (Poley. et al, 2022). Moreover, during breast cancer awareness month in Israel, we published a paper in Science Advances journal (Kaduri. et al, 2021) demonstrating that suppressing neurons in orthotopic triple-negative breast cancer tumors, inhibits pain, tumor growth, and metastatic dissemination.
The results derived from this ERC project were presented in above one hundred fifty conferences, scientific publications, general public lectures and online videos, expanding the dissemination and sparking much attention. A total of 18 papers describing the project's achievements have been published in leading peer-reviewed journals including Nature Nanotechnology, Nature Communications, and Science Advances, allowing their findings to be widely disseminated in the scientific community.
Using targeted nanotechnologies allowed rapid analysis of drug activity (96 hours) and ensured the system's safety by using minuscule doses (~1/1000 the therapeutic dose). During the project, we explored how different cell types in the tumor microenvironment and metastasis respond to medication and correlated this to genomic data.
During the ERC-StG research program period, we demonstrated for the first time that artificial particles that mimic natural cells, coined – synthetic cells (SC), containing the molecular machinery necessary for carrying out transcription and translation, were used to synthesize anti-cancer RNA biologics inside tumors (Krinsky. et al, 2016 and Krinsky. et al, 2018) and communicate with living cells through light (optogenetic) signals. These findings were recently published in Nature Communications (Adir. et al, 2022).
We also showed the importance of gender (patient’s sex) in nanomedicine design and the effect of nanoparticles accumulation in the female reproductive system on cancer treatment and fertility (Poley. et al, 2022). Moreover, during breast cancer awareness month in Israel, we published a paper in Science Advances journal (Kaduri. et al, 2021) demonstrating that suppressing neurons in orthotopic triple-negative breast cancer tumors, inhibits pain, tumor growth, and metastatic dissemination.
The results derived from this ERC project were presented in above one hundred fifty conferences, scientific publications, general public lectures and online videos, expanding the dissemination and sparking much attention. A total of 18 papers describing the project's achievements have been published in leading peer-reviewed journals including Nature Nanotechnology, Nature Communications, and Science Advances, allowing their findings to be widely disseminated in the scientific community.
This project has generated breakthrough technologies and expands the state of the art demonstrating that nanotechnology can be used as a new tool for facilitating personalized medicine. Conceptually, the project demonstrated that nanoparticles can be used for diagnosing drug activity, with single-cell precision. Furthermore, nanoparticles loaded with medicines were primarily used in the past for delivering drugs, rather than for the diagnosis of drug activity. Combined, with the advancement of the field, this project provides extremely valuable scientific findings in the field of cancer nanotechnology as well as medical promise to improve the care of patients with metastatic breast cancer.
I believe the Barcode technological platform will be translated to the clinic and will provide patients with an improved treatment approach, compared to the current ‘trial-and-error’ reality in the clinic, in which patients are receiving several treatments before determining the optimal treatment for them.
Light-based communication in synthetic cells is another intriguing outcome of the project that goes beyond the state of the art. We showed for the first time that synthetic nanoparticles can communicate with natural cells, and vice versa. We harness bioluminescence to engineer intercellular and intracellular signaling mechanisms in SCs for the purpose of activating cellular processes in both natural and synthetic cells (SCs).
I believe the Barcode technological platform will be translated to the clinic and will provide patients with an improved treatment approach, compared to the current ‘trial-and-error’ reality in the clinic, in which patients are receiving several treatments before determining the optimal treatment for them.
Light-based communication in synthetic cells is another intriguing outcome of the project that goes beyond the state of the art. We showed for the first time that synthetic nanoparticles can communicate with natural cells, and vice versa. We harness bioluminescence to engineer intercellular and intracellular signaling mechanisms in SCs for the purpose of activating cellular processes in both natural and synthetic cells (SCs).