At your side
to pioneer
immuno-oncology
therapies
We are a specialty contract research organization offering preclinical and translational research services for the development of novel anti-cancer immunotherapies.
Based in France, we have assisted international biotech and pharma companies, as well as comprehensive cancer centers for the past 10 years.
Our expertise in cancer immunotherapies
New paper : Faecalibaterium prausnitzii strain EXL01 boosts efficacy of immune checkpoint inhibitors
We're happy to showcase a collaboration just published in OncoImmunology. Since 2016, French biotech Exeliom Bioscience has been advancing therapeutic programs targeting the gut microbiota in Crohn's disease and various types of cancer, based on the immuno-modulatory bacterium Faecalibacterium prausnitzii (oral drug EXL01). In this paper, we supported Exeliom Bioscience in the generation of in vivo and vitro data to decipher the mechanism of action of EXL01.
The in vivo study, based on the MCA205 syngeneic tumor model, demonstrates that oral supplementation with EXL1 restores the efficacy of anti-PD-L1 immunotherapy in animals with antibiotics-induced gut dysbiosis. The subsequent in vitro investigation, based on the MLR assay, showed that the EXL1 strain boosts the activation of both dendritic cells and T cells in the presence of anti-PD-L1 antibody.
The in vivo study, based on the MCA205 syngeneic tumor model, demonstrates that oral supplementation with EXL1 restores the efficacy of anti-PD-L1 immunotherapy in animals with antibiotics-induced gut dysbiosis. The subsequent in vitro investigation, based on the MLR assay, showed that the EXL1 strain boosts the activation of both dendritic cells and T cells in the presence of anti-PD-L1 antibody.
Read the paper
From the 8th to the 14th of September, Gregory Lebras will run 330km in the Aosta Valley, in Italy. Enlisted for the TOR330 - TOR DES GÉANTS ultra-endurance trail together with 1,100 competitors, this anesthetist nurse at the Institut Bergonié Comprehensive Cancer Center aims to raise funds to support sarcoma research. Over 7 days, he will encourage his audience to make donations to the not-for-profit association "La Course du Petit Prince".
"We actively participate in the RHU Condor, a research consortium that receives funds from "La Course du Petit Prince" for the development of novel immunotherapies against soft-tissue sarcoma. So when we learned about the initiative of Gregory, we felt compelled to be part of it. Gregory is currently running over 10h per week, he's dedicated, fun, and generous. It just clicked. I can tell we are very proud sponsors !" Alban Bessede, CEO of Explicyte.
"We actively participate in the RHU Condor, a research consortium that receives funds from "La Course du Petit Prince" for the development of novel immunotherapies against soft-tissue sarcoma. So when we learned about the initiative of Gregory, we felt compelled to be part of it. Gregory is currently running over 10h per week, he's dedicated, fun, and generous. It just clicked. I can tell we are very proud sponsors !" Alban Bessede, CEO of Explicyte.
Make a donation
Alban Bessede, CEO of Explicyte, and Antoine Italiano, MD at the Institut Bergonié, were in Chicago in early June at the 2024 ASCO meeting to present a recent piece of research performed in partnership with 3 French Comprehensive Cancer Centers: Institut Gustave Roussy (Paris), Institut Bergonié (Bordeaux), and Institut Claudius Regaud (Toulouse).
In this phase II trial of Regorafenib (anti-VEGFR therapy) combined with avelumab (anti-PD-L1 immunotherapy) in soft-tissue sarcoma patients with cold tumors (TLS-negative), we found a positive effect of this combotherapy in terms of anti-tumor immunity mobilization and 6-month progression-free survival (PFS).
In this phase II trial of Regorafenib (anti-VEGFR therapy) combined with avelumab (anti-PD-L1 immunotherapy) in soft-tissue sarcoma patients with cold tumors (TLS-negative), we found a positive effect of this combotherapy in terms of anti-tumor immunity mobilization and 6-month progression-free survival (PFS).
Read abstract
Over the past 5 years, our translational team released major papers in the field of cancer immunotherapy, in collaboration with French oncologists from the Institut Bergonié and Gustave Roussy Comprehensive Cancer Centers. Here are 5 key papers to highlight what we've learned:
In patients with advanced Non-Small Cell Lung Cancer (NSCLC) treated with PD-L1 inhibitor atezolizumab, the overexpression of trophoblast cell surface antigen 2 (TROP2) is associated with poorer progression-free survival. TROP2High patients are more likely to benefit from a combination of immunotherapy and anti-TROP2 agents.
Technologies used: Plasma Proteomics, Bulk Transcriptomics, Digital Pathology (IF), Spatial Transcriptomics
Read paper
By analyzing NSCLC tumor samples from 891 patients treated with immune checkpoint inhibitors or chemotherapy, we evidenced that IDO1 expression was associated with a favorable clinical outcome (ORR, PFS, OS) upon ICI but not chemotherapy. We also demonstrated that IDO1 is overexpressed within inflamed tumors and noticeably in Tertiary Lymphoid Structures (TLS). These results strongly suggest that targeting the immunosuppressive IDO1 enzyme could be beneficial in patients with inflamed tumors.
Technologies used: T-cell Killing Assay, Germinal Center Reaction Assay, Bulk Transcriptomics, Digital Pathology (IHC/IF), Spatial Transcriptomics
Read paper
Metabolomic analysis of plasma samples collected before cancer patients underwent immunotherapy revealed that the presence of Acetaminophen (APAP) correlates with a limited response to immune checkpoint blockade. This negative impact was validated in two independent prospective cohorts and further strengthened by preclinical evidence, both in vitro and in vivo. Altogether, our findings suggest that the use of Acetaminophen, one of the most widely used drugs, limits cancer immunotherapy efficacy and should be taken with caution.
Technology used: Flow cytometry, Plasma Proteomics, In Vitro Assays, In Vivo Experiments
Read paper
We analyzed the presence of Tertiary Lymphoid Structures (TLS) in tumor samples from 328 patients with solid tumors treated with anti-PD1 or anti-PD-L1 monoclonal antibodies. We found that the presence of mature TLS is predictive of improved clinical outcome (objective response, progression-free survival, overall survival).
Technology used: Digital Pathology
Read paper
Using Olink-based proteomics, we analyzed the plasma samples of 387 patients with advanced cancer treated with immune checkpoint inhibitors. High levels of Leukemia inhibitory factor (LIF) emerged as indicative of poor clinical outcome. The study identifies LIF as a potential target to improve the efficacy of cancer immunotherapies.
Technology used: Plasma Proteomics
Read paper
That's it for now! If you wish to get a full picture of our scientific production, please take a look here.
And if you have a translational research project in mind, let's talk about it. We'll be happy to help.
In Clinical Cancer Research (2024): TROP2 is a biomarker of resistance to immune checkpoint inhibition in NSCLC
In patients with advanced Non-Small Cell Lung Cancer (NSCLC) treated with PD-L1 inhibitor atezolizumab, the overexpression of trophoblast cell surface antigen 2 (TROP2) is associated with poorer progression-free survival. TROP2High patients are more likely to benefit from a combination of immunotherapy and anti-TROP2 agents.
Technologies used: Plasma Proteomics, Bulk Transcriptomics, Digital Pathology (IF), Spatial Transcriptomics
Read paper
In Clinical Cancer Research (2023): IDO1 is a potential therapeutic target for NSCLC patients with inflamed tumor microenvironment and/or TLS
By analyzing NSCLC tumor samples from 891 patients treated with immune checkpoint inhibitors or chemotherapy, we evidenced that IDO1 expression was associated with a favorable clinical outcome (ORR, PFS, OS) upon ICI but not chemotherapy. We also demonstrated that IDO1 is overexpressed within inflamed tumors and noticeably in Tertiary Lymphoid Structures (TLS). These results strongly suggest that targeting the immunosuppressive IDO1 enzyme could be beneficial in patients with inflamed tumors.
Technologies used: T-cell Killing Assay, Germinal Center Reaction Assay, Bulk Transcriptomics, Digital Pathology (IHC/IF), Spatial Transcriptomics
Read paper
In Annals of Oncology (2022): Acetaminophen negatively impacts cancer immunotherapy efficacy
Metabolomic analysis of plasma samples collected before cancer patients underwent immunotherapy revealed that the presence of Acetaminophen (APAP) correlates with a limited response to immune checkpoint blockade. This negative impact was validated in two independent prospective cohorts and further strengthened by preclinical evidence, both in vitro and in vivo. Altogether, our findings suggest that the use of Acetaminophen, one of the most widely used drugs, limits cancer immunotherapy efficacy and should be taken with caution.
Technology used: Flow cytometry, Plasma Proteomics, In Vitro Assays, In Vivo Experiments
Read paper
In Nature Cancer (2021): The presence of mature TLS is a predictive biomarker of anti-PD1/PD-L1 axis blockers efficacy in patients with advanced cancer
We analyzed the presence of Tertiary Lymphoid Structures (TLS) in tumor samples from 328 patients with solid tumors treated with anti-PD1 or anti-PD-L1 monoclonal antibodies. We found that the presence of mature TLS is predictive of improved clinical outcome (objective response, progression-free survival, overall survival).
Technology used: Digital Pathology
Read paper
In Annals of Oncology (2021): Elevated LIF level in serum is a predictive biomarker of resistance to immune checkpoint inhibition
Using Olink-based proteomics, we analyzed the plasma samples of 387 patients with advanced cancer treated with immune checkpoint inhibitors. High levels of Leukemia inhibitory factor (LIF) emerged as indicative of poor clinical outcome. The study identifies LIF as a potential target to improve the efficacy of cancer immunotherapies.
Technology used: Plasma Proteomics
Read paper
That's it for now! If you wish to get a full picture of our scientific production, please take a look here.
And if you have a translational research project in mind, let's talk about it. We'll be happy to help.
New paper in Clinical Cancer Research! The result of a joint work between Bergonié Institute, Gustave Roussy Institute and Explicyte.
Relying on precious patient samples and cutting-edge technologies, the teams involved discovered that Trophoblast cell-surface antigen 2 (TROP2), well-known as an attractive target for antibody-drug conjugate (ADC)-based therapy, is a strong predictor of resistance to immunotherapy, but not to chemotherapy, in patients with advanced lung cancer.
Pr. Antoine Italiano (Bergonié and Gustave Roussy Institutes) supervised the entire study, which follows on previous research on tertiary lymphoid structures (more here). He shares his views on this outstanding work.
Read the article here, entitled “TROP2 is associated with primary resistance to immune checkpoint inhibition in patients with advanced non-small cell lung cancer”.
Why is TROP2 getting so much attention today?
Pr. Italiano: TROP2 emerges as a pivotal player in the realm of cancer research and therapy due to its overexpression in various cancer types (breast, lung, etc.). This high expression positions TROP2 as a promising biomarker for cancer detection but also as a prime target for therapeutic intervention.
The compelling narrative surrounding TROP2 is gaining further strength with the positive results of numerous studies evaluating the safety and efficacy of ADCs specifically designed to target TROP2. Tangible results have been achieved in breast, urothelial, and non-small cell lung cancer (NSCLC). These studies validate TROP2 targeting as a robust and successful strategy in the ongoing pursuit of effective cancer therapies.
In light of these substantial findings, TROP2 emerges as a beacon of hope and a focal point for future advances in cancer diagnosis and treatment.
What is the main result of your study? Can you comment on the link between TROP2 expression and the tumor microenvironment characteristics?
Pr. Italiano: The reason for the TROP2 upregulation in cancer cells remains unclear; however, it is postulated that TROP2 plays a crucial role in regulating cell proliferation and invasion. This suggests that its overexpression could selectively drive tumor progression. Notably, preclinical data support this hypothesis, demonstrating that TROP2 overexpression stimulates tumor growth, while TROP2 knockdown inhibits it.
Moreover, preclinical findings indicated that surface expression of TROP2 in lung cancer cells could impact the functionality of cancer cell reactive T cells, leading to apoptosis of CD8+ T cells. Intrigued by these observations, we sought to investigate the influence of TROP2 expression on treatment outcomes of NSCLC patients undergoing immunotherapy.
Our analysis of large independent patient cohorts revealed an association between TROP2 overexpression, NSCLC microenvironment, and response to immune checkpoint inhibitors. Specifically, NSCLC with low TROP2 expression had the highest abundance of immune cells, including T cells, cytotoxic lymphocytes, and B cells. Conversely, high expression of TROP2 was linked to primary resistance to immune checkpoint inhibitors. To our knowledge, this study represents the first correlation between TROP2 expression levels, tumor microenvironment, and patient outcomes.
What is the impact of this research on the clinical development of TROP2 ADC candidates?
Pr. Italiano: TROP2 targeting appears to be a very promising therapeutic strategy for patients with advanced NSCLC. Compelling results from the reference study (TROPION-Lung01) Phase III trial show the effectiveness of the main TROP2 ADC (Datopotamab deruxtecan, Dato-DXd) compared to Docetaxel, the current standard of care in chemotherapy, in NSCLC patients treated with at least one prior line of therapy.
Recent data indicate that combining TROP2 targeting with PD-1/PD-L1 inhibition yields promising responses and presents no new safety signals in patients with previously untreated advanced or metastatic NSCLC lacking actionable genomic alterations.
Building on our results, we hypothesize that patients most likely to benefit from this therapeutic strategy are those with high TROP2 expression. Notably, our finding of a strong correlation between circulating levels of TROP2 and its expression by tumor cells suggests that selection of these patients can be achieved non-invasively through a simple blood test.
This groundbreaking approach not only strengthens the potential of TROP2 as a key therapeutic target, but also introduces a practical and accessible method of patient stratification, paving the way for personalized and effective treatments at the forefront of NSCLC management.
How did Explicyte contribute to this major discovery?
Pr. Italiano: The collaboration with Explicyte teams played a pivotal role in the success of this study. Explicyte offers a unique and comprehensive immuno-oncology platform, seamlessly integrating robust analytical technologies, for groundbreaking testing of cancer immunotherapies. This includes cutting-edge capabilities in gene sequencing, spatial transcriptomics, multiplex immunofluorescence, plasma proteomics, and more.
Explicyte being installed within Bergonié Institute, this proximity allows our clinical and research teams to foster close collaborations with them. Undeniably, this proximity favors a synergistic approach to advance our understanding of cancer immunotherapies and translate these findings into meaningful clinical applications. The invaluable contributions offered by these collaborative efforts underscore the strength of our partnership in driving innovative advances in the field of immuno-oncology.
What are the remaining challenges to radically change the outcome of NSCLC?
Pr. Italiano: NSCLC poses a myriad of challenges due to its heterogeneous nature. A significant breakthrough lies in the development and validation of a platinum-free first-line regimen for patients with advanced NSCLC, free of adverse effects.
Our results present a compelling proposition in this regard. Combining TROP2 ADC with immune checkpoint inhibitors emerges as a promising strategy, while introducing a paradigm shift in how we approach the treatment of advanced NSCLC. To the extent that it eliminates platinum from the therapeutic landscape, it holds the promise of significantly improving the quality of life of patients facing this complex and demanding disease.
Relying on precious patient samples and cutting-edge technologies, the teams involved discovered that Trophoblast cell-surface antigen 2 (TROP2), well-known as an attractive target for antibody-drug conjugate (ADC)-based therapy, is a strong predictor of resistance to immunotherapy, but not to chemotherapy, in patients with advanced lung cancer.
Pr. Antoine Italiano (Bergonié and Gustave Roussy Institutes) supervised the entire study, which follows on previous research on tertiary lymphoid structures (more here). He shares his views on this outstanding work.
Read the article here, entitled “TROP2 is associated with primary resistance to immune checkpoint inhibition in patients with advanced non-small cell lung cancer”.
Why is TROP2 getting so much attention today?
Pr. Italiano: TROP2 emerges as a pivotal player in the realm of cancer research and therapy due to its overexpression in various cancer types (breast, lung, etc.). This high expression positions TROP2 as a promising biomarker for cancer detection but also as a prime target for therapeutic intervention.
The compelling narrative surrounding TROP2 is gaining further strength with the positive results of numerous studies evaluating the safety and efficacy of ADCs specifically designed to target TROP2. Tangible results have been achieved in breast, urothelial, and non-small cell lung cancer (NSCLC). These studies validate TROP2 targeting as a robust and successful strategy in the ongoing pursuit of effective cancer therapies.
In light of these substantial findings, TROP2 emerges as a beacon of hope and a focal point for future advances in cancer diagnosis and treatment.
What is the main result of your study? Can you comment on the link between TROP2 expression and the tumor microenvironment characteristics?
Pr. Italiano: The reason for the TROP2 upregulation in cancer cells remains unclear; however, it is postulated that TROP2 plays a crucial role in regulating cell proliferation and invasion. This suggests that its overexpression could selectively drive tumor progression. Notably, preclinical data support this hypothesis, demonstrating that TROP2 overexpression stimulates tumor growth, while TROP2 knockdown inhibits it.
Moreover, preclinical findings indicated that surface expression of TROP2 in lung cancer cells could impact the functionality of cancer cell reactive T cells, leading to apoptosis of CD8+ T cells. Intrigued by these observations, we sought to investigate the influence of TROP2 expression on treatment outcomes of NSCLC patients undergoing immunotherapy.
Our analysis of large independent patient cohorts revealed an association between TROP2 overexpression, NSCLC microenvironment, and response to immune checkpoint inhibitors. Specifically, NSCLC with low TROP2 expression had the highest abundance of immune cells, including T cells, cytotoxic lymphocytes, and B cells. Conversely, high expression of TROP2 was linked to primary resistance to immune checkpoint inhibitors. To our knowledge, this study represents the first correlation between TROP2 expression levels, tumor microenvironment, and patient outcomes.
What is the impact of this research on the clinical development of TROP2 ADC candidates?
Pr. Italiano: TROP2 targeting appears to be a very promising therapeutic strategy for patients with advanced NSCLC. Compelling results from the reference study (TROPION-Lung01) Phase III trial show the effectiveness of the main TROP2 ADC (Datopotamab deruxtecan, Dato-DXd) compared to Docetaxel, the current standard of care in chemotherapy, in NSCLC patients treated with at least one prior line of therapy.
Recent data indicate that combining TROP2 targeting with PD-1/PD-L1 inhibition yields promising responses and presents no new safety signals in patients with previously untreated advanced or metastatic NSCLC lacking actionable genomic alterations.
Building on our results, we hypothesize that patients most likely to benefit from this therapeutic strategy are those with high TROP2 expression. Notably, our finding of a strong correlation between circulating levels of TROP2 and its expression by tumor cells suggests that selection of these patients can be achieved non-invasively through a simple blood test.
This groundbreaking approach not only strengthens the potential of TROP2 as a key therapeutic target, but also introduces a practical and accessible method of patient stratification, paving the way for personalized and effective treatments at the forefront of NSCLC management.
How did Explicyte contribute to this major discovery?
Pr. Italiano: The collaboration with Explicyte teams played a pivotal role in the success of this study. Explicyte offers a unique and comprehensive immuno-oncology platform, seamlessly integrating robust analytical technologies, for groundbreaking testing of cancer immunotherapies. This includes cutting-edge capabilities in gene sequencing, spatial transcriptomics, multiplex immunofluorescence, plasma proteomics, and more.
Explicyte being installed within Bergonié Institute, this proximity allows our clinical and research teams to foster close collaborations with them. Undeniably, this proximity favors a synergistic approach to advance our understanding of cancer immunotherapies and translate these findings into meaningful clinical applications. The invaluable contributions offered by these collaborative efforts underscore the strength of our partnership in driving innovative advances in the field of immuno-oncology.
What are the remaining challenges to radically change the outcome of NSCLC?
Pr. Italiano: NSCLC poses a myriad of challenges due to its heterogeneous nature. A significant breakthrough lies in the development and validation of a platinum-free first-line regimen for patients with advanced NSCLC, free of adverse effects.
Our results present a compelling proposition in this regard. Combining TROP2 ADC with immune checkpoint inhibitors emerges as a promising strategy, while introducing a paradigm shift in how we approach the treatment of advanced NSCLC. To the extent that it eliminates platinum from the therapeutic landscape, it holds the promise of significantly improving the quality of life of patients facing this complex and demanding disease.
We have developed and validated a mixed leukocyte reaction assay which is based on a co-culture of allogenic CD4+ T cells and monocyte-derived DCs.
Discover our latest publication, featured in Clinical Cancer Research!
Our in vitro macrophage-based assays are relevant to assess immunotherapeutics and question their mechanisms of action.
Conversing with Professor Antoine Italiano, a worldwide expert on early drug development, phase I oncology trials and immuno-oncology, upon the release of a recent article in Clinical Cancer Research.
Explicyte Immuno-Oncology I Cancer ImmunoTherapy CRO Services
Explicyte immuno-oncology offers preclinical contract research services for cancer immunotherapy drug discovery and translational research services. Our preclinical CRO services range from cell-based assays – for the phenotypic screening of novel immunotherapeutics and the in vitro determination of the molecular mechanism of action of new anti-cancer immune modulators – to in vivo studies, using syngeneic mouse tumor models treated with antitumor immunotherapies such as immune checkpoint inhibitors (anti-CTLA-4 monoclonal antibodies, anti-PD1/PDL-1 antibody therapy). Furthermore, we offer to explore the in vivo mechanism of action of innovative immunotherapies such as anti-cancer vaccines, gut microbiota modulators, and CAR-T and NK cell therapies, through the profiling of the anti-tumor immune response by flow cytometry, quantitative digital pathology, and RT-qPCR. In addition, we provide translational services in immuno-oncology. Working with patient biopsies (liquid or solid samples), we can assist clinicians in the discovery of novel cancer targets and biomarkers of cancer immunotherapies. In the context of clinical trials, we offer biomarker testing and biomarker research services. Our flow cytometry team has a 10-year expertise in biomarker analysis in plasma, serum, and PBMC samples. We also offer to analyze tumor biopsies using digital pathology, spatial transcriptomics, and Olink-based proteomics. All our drug development services for cancer immunotherapy are performed in Bordeaux, France, serving clients all around the world, including sponsors in Europe (EU and outside), Germany, Belgium, Spain, UK, USA, Canada, Japan, and Korea.