Optimized CAR-T cells, vaccinotherapy, super-responders, improved oncogenetic follow-up... the promising advances of Institut Curie at the AACR Congress 2026

Just ahead of the AACR meeting, Institut Curie will also take part in the C8 Early Career Symposium in San Diego, an event dedicated to showcasing cutting-edge advances in cancer biology and translational research. On April 16th and 17th, Dr. Gudrun Schleiermacher, pediatric oncologist and researcher at Institut Curie, will mentor several roundtables, while 
Dr. Marianne Burbage, researcher at Institut Curie, will present her work on targeting splicing machinery to modulate tumor immunogenicity. Through its participation in the C8 Symposium, a group composed of world-class cancer research centers coming together to promote collaboration and interaction among scientists, Institut Curie is reinforcing its role at the heart of global collaboration, aiming to accelerate discoveries for the benefit of patients living with cancer.

Oncogenetics: A New Approach to Managing Genetic Predispositions to Colon Cancer

With more than 7,000 consultations per year, Institut Curie is the specialized center carrying out the most oncogenetic consultations in France. The research carried out by Institut Curie in this field is recognized at the highest international level—evidenced by the oral presentation of Dr. Keltouma Driouch, an engineer in the Genetics Department of Institut Curie.

When a genetic predisposition to cancer is suspected, a blood test is most often performed to detect a mutation inherited from one of the two parents and transmitted to all the cells of the organism (constitutional mutation). If the blood tests do not reveal any genetic alteration, a team from Institut Curie demonstrates the importance of continuing genetic analysis with a tissue approach in patients with polyposis (pathology characterized by the presence of a high amount of polyps, precursor lesions of colon cancer) in search of genetic alterations called "mosaic" in the tissues themselves. Such alterations, acquired at the beginning of the individual's embryonic development, at a stage more or less prior to fecundation, are called “post-zygotic”. Therefore, there are neither inherited from the parents nor present in all the cells (thus escaping the blood analysis).

"This tissue approach requires a complex, long, and tedious working process. Among the 120 patients included in our study, 60 were unable to obtain a result regarding a mosaic alteration due to an insufficient number of received and analyzable samples. However, our efforts have proven to pay off since, in a third of the "informative" cases (or about 20 people), a genetic alteration in mosaic has been identified ," explains Dr. Bruno Buecher, gastroenterologist and oncogenetician at Institut Curie. 

These results have a direct and major impact on the follow-up and monitoring of patients (in particular on the rhythm of colonoscopies). They are also redefining genetic counseling for families: in these "mosaic" situations, the ascendants and collateral relatives (parents, brothers, sisters, uncles, aunts, nephews, nieces or cousins) can be reassured. On the other hand, a targeted test can be proposed to the descendants who will have to undergo a specific colonoscopic screening if the alteration is detected.

The Institut Curie team went even further in the analysis by showing that in some polyps, the genetic mutation was due to an infection with the bacterium E. coli, capable of producing colibactin (a genotoxic substance). "Colon cancers can be caused by constitutional genetic alterations, mosaic alterations and/or be linked to a bacterial infection," explains Dr. Keltouma Driouch. Better understanding the genetic (inherited or not) or infectious origins of colorectal adenomatous polyposes allows us to better manage, follow up and monitor patients and their relatives.

ORAL PRESENTATION APC mosaicism and colibactin-associated signature as key factors in unexplained colorectal polyposis - Bruno Buecher, Keltouma Driouch. - Mini-Symposium Prevention / Early Detection / Interception. April 2026

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Pediatric Cancer: Blood Tests to Improve Care for Children with High-Risk Neuroblastoma 

With 130 to 150 new cases identified each year in France, neuroblastoma is the second most common solid tumor in children. However, the effectiveness of the treatments remains limited, especially in the high-risk form, which is very aggressive.

The teams of Institut Curie have acquired a world-renowned expertise in the research and management of neuroblastoma; thanks, in particular, to the research carried out by Dr. Gudrun Schleiermacher, pediatrician and deputy director for translational research of the SIREDO Center (Care, Innovation, Research in Oncology of Children, Adolescents and Young Adults) from Institut Curie. She develops approaches combining multi-omics analyses (genomics, transcriptomics, proteomics, metabolomics, etc.), starting from the tumor but also from circulating tumor DNA (ctDNA) to better understand the evolution of the disease and the mechanisms of resistance in order to adapt treatments. In this context, she will present the results of two flagship European studies in high-risk neuroblastoma (BEACON-Bio and MICCHADO).

Monitoring tumor evolution and resistance to treatment in real time

The European BEACON-Bio study aims to better understand the biological mechanisms involved in relapses in young patients with high-risk neuroblastoma treated in the BEACON study (BEyACizumab added to temozolomide ± IrinOtecan for children with refractory/relapsed Neuroblastoma). As part of this Phase 2 trial, the researchers showed that the amount of circulating tumor DNA is associated with the clinical course of the disease. In addition, new mutations of a certain RAS/MAPK signaling pathway - markers of resistance to treatment - are found in about a quarter of patients and, in some, appear during the course of treatment. This is the first time that these mutations have been identified in the blood of patients, revealing – in real time - resistance mechanisms that were previously imperceptible and correlated with a poorer prognosis. These data suggest that a plasma analysis, carried out throughout the follow-up of patients, could become a useful indicator of the clinical evolution of tumors. Especially since these liquid biopsies, carried out by a simple blood test, are not invasive.

Better characterize the tumors of young patients from the moment of diagnosis 

Between 2018 and 2024, the extensive European study MICCHADO (Molecular and Immunological Characterisation of high risk CHildhood cancer At DiagnOsis), sponsored by Institut Curie, enrolled 599 patients—including 190 young patients with neuroblastoma—with the objective of establishing a molecular and immunological characterization of this cancer, and subsequently identifying biomarkers correlated with relapse. Researchers analyzed several types of biomarkers, such as circulating DNA levels and alterations, as well as immune cell populations. 

They observed higher levels of circulating tumor DNA in patients with high-risk neuroblastoma, compared to those with low-risk forms. Analyses also revealed specific alterations in circulating DNA at the time of relapse, confirming the value of this approach for tailoring treatment. Moreover, this work highlights biological profiles associated with an increased risk of relapse, in particular, variations in immune cell populations.

"Our research highlights the complementarity between tumor biopsy and liquid biopsy and paves the way for personalized and adaptive medicine, directing patients to more targeted therapies according to the evolution of their disease," asserts Dr. Gudrun Schleiermacher. Beyond bringing together research and clinical care teams, Institut Curie’s strength lies in promoting large-scale studies—at both the European and international levels—for these pediatric cancers, which require heightened coordination. And it is precisely this synergy that drives us to accelerate discoveries to change the way our young patients are cared for."

ORALPRESENTATION  Sequential cell free DNA analysis reveals genetic heterogeneity in patients with relapsed neuroblastoma enrolled in the SIOPEN-ITCC BEACON study - session Pediatric Cancer from Mechanism to Translation.Dr. Gudrun Schleiermacher,  April 20 2026

POSTER – Multi-omics profiling of neuroblastoma identifies immunological biomarkers associated with higher risk of relapse: Results from the MICCHADO study –Dr. Gudrun Schleiermacher, session Integrative Computational Approaches. April 20 2026

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The very promising results of new "optimized" CAR-T in primary oculocerebral lymphoma

Cell and gene therapies, most notably CAR-T (Chimeric Antigen Receptor T-cells) cells, are becoming increasingly important in cancer treatment. An integral part of the therapeutic arsenal against certain hematological tumors, more effective strategies and more numerous indications are being explored, including in solid tumors.

At Institut Curie, the team led by Dr. Marion Alcantara, hematologist and medical director of the cell and gene therapies platform of the PSCC at Institut Curie CellAction, conducted research, in collaboration with Mnemo Therapeutics, about a new form of "optimized" CAR-T cells in a preclinical model of primary oculocerebral lymphoma, a rare and aggressive hematological cancer that develops in the central nervous system. 

The objective of this study was to evaluate these CAR-T of a new kind based on an immuno-epigenetics strategy developed for more than ten years by the teams of Institut Curie. "Increased functional persistence, better tumor control and prevention of relapses, the preclinical results obtained in our primary oculocerebral lymphoma models are excellent and reveal the effectiveness of our optimized CAR-T, much higher than that of conventional CAR-T ," declares Dr. Marion Alcantara. 

These very promising results pave the way for the launch of a Phase I/II clinical trial in patients with relapsed/refractory primary oculocerebral lymphoma. If this clinical study validates the proof of concept for this new approach, future clinical applications in other cancers could be envisaged.

POSTER Epigenetic and signaling-based engineering enhances CAR -T cell function in oculo-cerebral lymphoma – Dr. Marion Alcantara Dr. Jaime Fuentealba, adoptive Cell Therapy Session - April 20 2026

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Pancreatic Cancer: A New Family of Immune Cells Discovered in "Super-Responders"

In March 2026, the phase 2 results of the POLAR clinical trial conducted in the United States showed the effectiveness of adding immunotherapy to targeted therapy in patients with metastatic pancreatic cancer*. 

Novel Research led by Dr. Marc Hilmi, medical oncologist at Institut Curie and post-doctoral fellow at the Memorial Sloan Kettering Cancer Center in New York, is presented at the AACR 2026 Congress: for the first time, research explains why immunotherapy is particularly effective in some patients while it is not in others. 

"We have identified a category of lymphocytes, the TIE (for T Infiltrated Expandable) present in the 10% of patients in the POLAR study—the super-responders—who reacted very well to immunotherapy and whose survival was exceptional ," declares Dr. Marc Hilmi. This discovery was made possible through novel spatial transcriptomics and single-cell analyses, enabling the precise characterization of cells based on their location within tissues.

The study showed that these TIE lymphocytes are able to expand in the blood and infiltrate the tissue near the tumor. But above all, the researchers reveal the presence of these singular cells at the time of diagnosis, thus proving that the immunity of the "super-responders" is pre-existing to any treatment. 

"Based on these results, the presence or absence of these TIE lymphocytes should make it possible to predict the response to immunotherapy in pancreatic cancer and possibly in other cancersas well, which is something we are still yet to explore…" concludes Dr. Marc Hilmi.

 

Caption: Spatial visualisation of TIE lymphocytes in contact with tumor cells in pancreatic cancer. Left: tumor tissue at the time of diagnosis, prior to treatment. Right: tumor tissue after two months of treatment in the POLAR trial. 

Tumor cells are shown in red and TIE lymphocytes in green. These images, obtained using cutting-edge technologies (spatial transcriptomics at the single-cell level), show that TIE lymphocytes are able to localise in the immediate vicinity of tumor cells. In so-called ‘super-responders’, these immune cells are already present at the time of diagnosis and persist throughout treatment. This proximity suggests that TIE lymphocytes play a key role in tumor recognition and control, explaining why some patients respond particularly well to immunotherapy.

 

POSTER - Invigorating pre-existing tumor-infiltrating expandable (TIE) T cell clonotypes in exceptional responders with dual PARP-PD-1 blockade in homologous recombination deficient (HRD) pancreatic cancer  – Dr Marc Hilmi, session Late-Breaking Research: Clinical Research- April 22 2026

* Pembrolizumab and olaparib in homologous-recombination-defective metastatic pancreatic cancer: phase 2 POLAR trial. Nature Medicine. March 25, 2026

What is pancreatic cancer ?

Towards a Therapeutic Vaccine Against Metastatic Uveal Melanoma

With 500 new cases diagnosed each year in France, uveal melanoma is the most common malignant eye tumor in adults. In 30 to 40% of cases, it becomes metastatic, especially in the liver. 

With the exception of tebentafusp*—a novel bispecific antibody (reserved for a specific category of patients)—immunotherapy is, to date, not very effective in the treatment of metastatic uveal melanoma.

At Institut Curie, the national referral center for this rare cancer, the teams are working to understand the genetic factors involved and to identify molecules specific to tumor cells (called "neo-antigens") that could be used for the development of therapeutic vaccines and other forms of immunotherapies.

In this context, researchers from Institut Curie have achieved a very thorough characterization of a certain family of immune cells: CD8+ T lymphocytes in the blood of patients and at the level of metastases. These CD8+ T cells are capable of recognizing and destroying tumor cells that present specific antigens. They discovered that CD8+ infiltrate, proliferate in tumors and circulate in the blood of metastatic patients of the M3 group (those whose tumor cells have lost a copy of chromosome 3, particularly metastatic). 

"This study highlights a specific immune response against tumors, detectable both in the liver and in the blood. The question is to know which are the antigens recognized by CD8+ that could be exploited to develop targeted treatments against metastases," declares Dr. Sol Yanel Nunez, postdoctoral fellow at Institut Curie, in the Immunity and Cancer Unit (Institut Curie, Inserm). Today we have succeeded in establishing a list of neo-antigen candidates specific to uveal melanoma and common to all patients. We are continuing our work to demonstrate that CD8+ T lymphocytes are capable of recognizing these neo-antigens and destroying uveal melanoma tumor cells in vitro. "This would enable us to validate our list of candidates and, ultimately, to develop a therapeutic vaccine or cell therapies that could benefit all patients."
 

POSTER Anti-tumor antigen CD8 T cells infiltrating M3 uveal melanoma metastases are detectable in the blood. Dr. Sol Y. Nunez, Dr. Ana I. Lalanne – Adaptive Immunity in Cancer session April 21 2026

* It should be noted that research involving Dr. Sophie Piperno-Neumann, medical oncologist at Institut Curie, on the 5-year survival results with tebentafusp for patients with metastatic uveal melanoma will be presented orally at the AACR Congress on April 19th, during the Advanced Cellular and Immune-Based Therapeutics session. 
 

New Biomarkers to Predict Response to Immunotherapies in Head and Neck Cancers

The sixth most common cancer in the world, ENT cancer affects 19,000 new patients each year in France. Although treatments are progressing in particular thanks to immunotherapy, it is only effective for about 20% of patients. The identification of predictive biomarkers of the response or resistance to immunotherapy in ENT cancers is therefore a major challenge. 

For this, Institut Curie coordinates a multi-omics study, in collaboration with the Leon Berard Center, Gustave Roussy, the University Cancer Institute of Toulouse Oncopole, the Valrose Institute of Biology and Unicancer. 
The researchers analyzed 183 samples from tumors of patients with advanced ENT cancers (from two clinical trials promoted by Unicancer - TOPNIVO and CHECK-UP). 

The congress will present for the first time the preliminary results of this study on the first two omics: genomics and transcriptomics. "Our genomic analyses reveal a link between mutations in the FAT-1 and TERT genes and patient survival. In addition, the analysis of the transcriptome allowed us to highlight two signatures consisting of approximately twenty genes, each correlated with the response to immunotherapy," explains Professor Ivan Bièche, Director of the Tumor Genomic Unit in the Genetics Department of Institut Curie. 

This is the first time that such DNA and RNA signatures have been identified in ENT cancers, thus opening up clinical prospects for customizing immunotherapy treatments and therapeutic de-escalation for patients.
These works initiated in 2021 are carried out within the framework of the SIGN'IT call for projects funded by the ARC Foundation.

POSTER -Transcriptomic and genomic signatures associated with response or resistance to immunotherapy (IO) in locally advanced/metastatic (LA/M) head and neck squamous cell carcinoma (HNSCC) patients. Dr. Elodie Girard, Dr. Ivan Bièche - session Biomarkers Predictive of Therapeutic Benefit 2 – April 19 2026