mixed leukocyte reaction assay
Reference: SM0624
Contract type: Full time position, permanent contract
Location: Bordeaux, France

 

You are passionate about the interplay between immune and tumor cells? You have experience with 2D and 3D models? You master flow cytometry and other multiparametric platforms for in vitro analysis? The perspective of testing innovative cancer immunotherapies creates some excitement? Keep reading and apply!


Keep reading and apply!

 

About Explicyte


Explicyte is a preclinical and translational contract research organization specialized in immuno-oncology. Our goal is to assist academics, biotechs, and pharmas in the discovery of novel targets and novel cancer immunotherapies.

With a team of 25, we’re a human-sized company, which brings under the same roof cell biologists, immunologists, in vivo scientists, medical oncologists, and bioinformaticians. Focused on sponsors’ projects, our activity also involves in-house R&D and external collaborations, which led to the publication of 25+ papers in high-impact-factor journals.

Based in Bordeaux, our lab is located at the Bergonié Comprehensive Cancer Center, where we work in close contact with medical oncology teams. We believe Explicyte is a place to learn, grow, and have impact in the fight against cancer.

More about us

 

Your position


To strengthen and expand our in vitro team and activities, we are looking for an experienced in vitro Immuno-Oncology Scientist, ready to take up with us the setup of new in vitro platforms and assays, relevant for the testing and development of novel immunotherapeutic strategies.

In your role, you will be responsible for the technical and organizational management of sponsors’ and in-house R&D in vitro studies, from their implementation and performance to data analysis. You will timeously provide deliverables with respect to the project’s requirements and timelines.

You will interact closely with the in vitro team members, and will report to study directors and to the CSO.

What you will find at Explicyte

 

Your skills & traits



  • Ph.D - or equivalent - in science and health-related field

  • Minimum 2 years of experience in preclinical development in the health industry: Pharma, Biotech, CRO…

  • Broad understanding of tumor immunology and/or cancer therapies

  • Expertise in cell culture protocols (eg. 2D, 3D, immune/tumor cell co-cultures, immune cell isolation and cultivation, differentiation and polarization protocols)

  • Mastery of multiparametric analysis methodologies, mainly in flow cytometry

  • Project management experience (from planning to closing projects)

  • Excellent diligence

  • Strong interpersonal & organizational skills

  • Ability to easily adapt to changing priorities and challenges

  • Enthusiasm, curiosity, and integrity


 

Your missions & responsibilities



  • Provide draft protocols according to the proposed scientific and experimental strategies

  • Implement studies - relying on undeniable organizational skills - according to their design and established schedules

  • Manage and perform - diligently - in vitro and ex-vivo experiments

  • Cell culture-based experiments for functional immuno-oncology assays: with human and rodent cell origins, with tumor and/or immune cells (PBMCs, T cells, macrophages, tumor-infiltrating leukocytes…), and requiring immune cell isolation and cultivation, differentiation, polarization, etc

  • 3D approaches: spheroids, organoids, and patient-derived tumor samples and their use in preclinical research and therapeutic assessment

  • Ex vivo processing of collected samples for immune or tumor cell isolation, or for further analyses (FACS, ELISA…)

  • Capture, analyze and compile data, including quality controls

  • Ensure accuracy and completeness of study documentation and timely provide study deliverables

  • Write internal protocols and standard operating procedures

  • Contribute to experimental development by implementing new methods and training other collaborators and team’s members


 

Apply now! 


 

in vivo efficacy studies syngeneic tumor models CRO services
Reference: SM0524
Contract type: Full time position, permanent contract
Location: Bordeaux, France

 

You’re an accredited animal experimentalist with a passion for immune response mechanisms? You have experience with in vivo models for immuno-oncology? You master flow cytometry and other platforms for ex vivo analysis? The perspective of testing innovative cancer immunotherapies creates some excitement?


Keep reading and apply!

 

About Explicyte


Explicyte is a preclinical and translational contract research organization specialized in immuno-oncology. Our goal is to assist academics, biotechs, and pharmas in the discovery of novel targets and novel cancer immunotherapies.

With a team of 25, we’re a human-sized company, which brings under the same roof cell biologists, immunologists, in vivo scientists, medical oncologists, and bioinformaticians. Focused on sponsors’ projects, our activity also involves in-house R&D and external collaborations, which led to the publication of 25+ papers in high-impact-factor journals.

Based in Bordeaux, our lab is located at the Bergonié Comprehensive Cancer Center, where we work in close contact with medical oncology teams. We believe Explicyte is a place to learn, grow, and have impact in the fight against cancer.

More about us

 

Your position


To strengthen our in vivo preclinical activities, we are looking for an experienced in vivo Immuno-Oncology Study Manager, ready to take up with us the implementation of projects and their protocols, relevant for the testing and development of novel immunotherapeutic modalities.

In your role, you will be responsible for the technical and organizational management of sponsors’ and in-house R&D in vivo studies, from their implementation and performance to data analysis. You will timeously provide deliverables with respect to the project’s requirements and timelines.

You will closely interact with the in vivo team members. You will report to the Study Directors and CSO.

What you will find at Explicyte

 

Your skills & traits



  • Ph.D - or equivalent - in science and health-related field

  • •Accreditation in animal experimentation level 1/2 is mandatory, ethical standards and regulations

  • Deep knowledge and mastery of preclinical tumor-bearing mouse models

  • Expertise in tissue collection and processing for flow cytometry-based analysis

  • •Knowledge in the fields of tumor immunology and cancer therapies

  • •Minimum 1-2 years’ experience in in vivopreclinical development in a health industry: Pharma, Biotech, CRO…

  • Project management experience (from planning to closing projects)

  • Excellent diligence

  • Strong interpersonal & organizational skills

  • Ability to easily adapt to changing priorities and challenges

  • Enthusiasm, curiosity, and integrity


 

Your missions & responsibilities



  • Provide draft protocols according to the proposed scientific and experimental strategies

  • Implement studies - relying on undeniable organizational skills - according to their design and established schedules

  • Manage and perform - diligently - in vivo and ex vivo experiments

  • Tumor cell line culture and maintenance

  • Mastery of anesthesia and surgical gestures

  • Tumor cell inoculation (subcutaneous, intradermic, intracranial, mammary fat pad, intrasplenic, etc.)

  • In vivo monitoring: tumor growth (physical, bioluminescence), body weight and survival, tolerability evaluation

  • Mastery of neuro-oncology related in vivo protocols and models is a plus

  • Treatment administration (oral, intraperitoneal, intravenous, intratumoral)

  • Sampling of biological tissues (blood, tumor, lymph nodes, organs)

  • Ex vivo processing of collected samples for immune or tumor cell isolation, or for further analyses (FACS, ELISA…)

  • Capture, analyze and compile data, including quality controls

  • Ensure accuracy and completeness of study documentation and timely provide study deliverables

  • Write and submit animal referrals for ethical committee approval

  • Write internal protocols and standard operating procedures


 

Apply now! 


 

TROP2 lung cancer
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.
mixed leukocyte reaction assay
In the context of cancer immune surveillance, dendritic cells (DCs) are key immune cells as they possess a unique ability to prime and expand antigen-specific CD4 and CD8 T cells. While trafficking from the tumor to the draining lymph nodes, they can cross-present tumor antigens and initiate a specific anti-tumor immune response. Even though several subsets exist, DCs must receive an activating signal to initiate a process of maturation that converts them from an accumulation to an antigen presentation mode to finally promote immunity or tolerance depending on the nature of the stimulus.

Thus, considering the importance of DCs in fine-tuning T cell response, their manipulation represents an attractive approach to elicit or boost an anti-tumor immune response. For this purpose, benefiting from a robust assay that evaluates the function and immunomodulation of DCs is highly valuable.

To this end, we have developed and validated a mixed leukocyte reaction (MLR) assay which is based on a co-culture of allogenic CD4+ T cells (responder) and monocyte-derived DCs (stimulator). The data shown here, originating from independent donor pairs, illustrate stimulatory or immunosuppressive properties of reference compounds. Indeed, while Adenosine, a well-known immunomodulatory nucleoside, favored a “tolerogenic” profile that translated into a limited MLR response as shown through lower levels of cytokines released in the co-culture, Nivolumab application significantly boosted the MLR response.

Hence, this dataset underlines the effectiveness of our assay in addressing the ability of test items to modulate DC-mediated immune responses.



Figure MLR VF

 

MLR in allogenic human mDC/CD4 T cell co-cultures from independent donor pairs is enhanced upon PD1 inhibition and limited by Adenosine.

Isolated peripheral blood monocyte-derived DCs are co-cultured with allogenic CD4+ T cells. At the end of the co-culture period, IFNg (A) and IL2 (B) levels released in the supernatants are measured by HTRF.

While mature DCs display T-cell stimulating ability underlined through the MLR response, this response is further optimized following PD1 blockade with Nivolumab and limited upon Adenosine treatment.

 

More about our MLR assays
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