Description du sujet de thèse

Characterization of the cellular and immunological mechanisms induced by a ribonucleoprotein-based vaccine targeting telomerase (TERT) in the context of anticancer immunotherapy

Contexte de travail

Scientific context:
Therapeutic cancer vaccines struggle to induce effective immune responses, mainly due to immune tolerance toward self-antigens. Ribonucleoproteins (RNPs), such as those formed by TERT and TERC RNA, have a unique capacity to break this tolerance through the combined activation of BCR/TLR receptors. The RNPVAX team has demonstrated the effectiveness of this vaccine in mice and in dogs with spontaneous tumors.

Thesis objectives:

Identify the key antigen-presenting cells (APCs) involved in the activation of T-cell responses induced by the TERT-RNP vaccine.

Define the innate signaling pathways (TLRs, interferons) involved in RNP recognition.

Characterize the adaptive immune response in vivo (Th1/Th2 profile, CD4/CD8 responses).

Study the effect of different RNP structures (monomers, multimers, chaperone-bound complexes) on immune efficacy.

Proposed methodology:

Immunophenotyping (flow cytometry) to identify responsive immune subpopulations.

ELISPOT / ELISA assays to quantify antigen-specific T-cell responses.

In vivo cell depletions (anti-CD4, CD8, B220, NK1.1, etc.) to validate key effectors.

Use of syngeneic mouse models (TC-1) to evaluate therapeutic effects.

Analysis of TLR signaling using reporter cell lines and RNA-FISH.

Scientific supervision:
Dr Patrick Brest & Dr Kellermann (IRCAN, immunology, signaling)
Collaboration with Dr Magali Blaud & Prof Nicolas Leulliot for structural RNP aspects (Université Paris Cité / CiTCoM)

Expected results:

Identification of immune signatures associated with an effective vaccine response.

Clarification of the role of different cell types in cross-presentation.

Preclinical data useful for optimizing vaccine formulations for clinical trials.

This project will be conducted at the Institute for Research on Cancer and Aging, Nice, France (IRCAN) and at the RespirERA IHU, both equipped with well-established and recognized technological platforms, in vivo and ex vivo experimental models, and human samples.
Our team is multidisciplinary, with 3 professor-physicians, 2 associate professors, 2 hospital practitioners, 4 CNRS or INSERM researchers, PhD students and master's students, ensuring a direct link between biology and clinical applications.
Our team is part of IRCAN INSERM U1081 / CNRS 7284, hosted within the Antoine Lacassagne Cancer Research Center in Nice, France. IRCAN, created on 1 January 2012 and directed by Prof Eric Gilson (INSERM Grand Prize 2019), is a Joint Research Unit overseen by the University of Nice, CNRS and Inserm.
IRCAN has established partnerships with the A. Lacassagne cancer center and the Nice University Hospital. Research at IRCAN is resolutely innovative, aiming to understand biological mechanisms linking aging and cancer, with particular emphasis on the role of stress, whether linked to the environment or lifestyle. New preventive tests, diagnostic tools, and therapies are expected to improve the treatment of cancers of various tissue origins and age-related diseases such as certain forms of diabetes, kidney failure, and cardiovascular disorders. This approach uniquely bridges fundamental questions of modern biology with major societal and public health challenges posed by population aging.
Our laboratory includes around fifteen researchers and operates in a dynamic, international environment. The candidate will also benefit from IRCAN's broader scientific environment (about 15 teams and 100 people dedicated to research on cancer and aging) and its shared technological platforms.

Contraintes et risques

We are looking for a highly motivated candidate with a Master's degree in biology, or a highly motivated and dynamic scientist. The candidate must hold at least a Master 2 in molecular and cellular biology. Experience in cell culture, manipulation of gene expression, as well as classical molecular and cellular biology techniques, and particularly familiarity with CRISPR tools, will be considered a positive asset.