A5035378552- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Single-cell and spatial transcriptomics
- Virus-based gene therapy research
- Immune Cell Function and Interaction
- Biosimilars and Bioanalytical Methods
- Immune cells in cancer
- Microbial metabolism and enzyme function
- Chemokine receptors and signaling
- Cancer Research and Treatments
- Ubiquitin and proteasome pathways
- Endoplasmic Reticulum Stress and Disease
- Cutaneous Melanoma Detection and Management
- Chronic Lymphocytic Leukemia Research
- Glycosylation and Glycoproteins Research
- Wnt/β-catenin signaling in development and cancer
University of Lausanne
2020-2024
Ludwig Cancer Research
2020-2024
Swiss Cancer Center Léman
2024
University Hospital of Lausanne
2020-2023
École Polytechnique Fédérale de Lausanne
2017
Abstract Expansion of antigen-experienced CD8 + T cells is critical for the success tumour-infiltrating lymphocyte (TIL)-adoptive cell therapy (ACT) in patients with cancer 1 . Interleukin-2 (IL-2) acts as a key regulator cytotoxic functions by promoting expansion and capability 2,3 Therefore, it essential to comprehend mechanistic barriers IL-2 sensing tumour microenvironment implement strategies reinvigorate responsiveness antitumour responses. Here we report that prostaglandin E2 (PGE 2...
The success of cancer immunotherapy depends in part on the strength antigen recognition by T cells. Here, we characterize cell receptor (TCR) functional (antigen sensitivity) and structural (monomeric pMHC-TCR off-rates) avidities 371 CD8 clones specific for neoantigens, tumor-associated antigens (TAAs) or viral isolated from tumors blood patients healthy donors. cells exhibit stronger avidity than their counterparts. Relative to TAA, neoantigen-specific are higher and, consistently,...
Adoptive cell therapy (ACT) using ex vivo–expanded tumor-infiltrating lymphocytes (TILs) can eliminate or shrink metastatic melanoma, but its long-term efficacy remains limited to a fraction of patients. Using longitudinal samples from 13 patients with melanoma treated TIL-ACT in phase 1 clinical study, we interrogated cellular states within the tumor microenvironment (TME) and their interactions. We performed bulk single-cell RNA sequencing, whole-exome spatial proteomic analyses pre-...
The identification of patient-specific tumor antigens is complicated by the low frequency T cells specific for each antigen. Here we describe NeoScreen, a method that enables sensitive rare (neo)antigens and cognate cell receptors (TCRs) expressed tumor-infiltrating lymphocytes. transduced with antigen-specific TCRs identified NeoScreen mediate regression established tumors in patient-derived xenograft mice.
The accurate selection of neoantigens that bind to class I human leukocyte antigen (HLA) and are recognized by autologous T cells is a crucial step in many cancer immunotherapy pipelines. We reprocessed whole-exome sequencing RNA (RNA-seq) data from 120 patients two external large-scale neoantigen immunogenicity screening assays combined with an in-house dataset 11 identified 46,017 somatic single-nucleotide variant mutations 1,781,445 neo-peptides, which 212 178 neo-peptides were...
T cell receptor (TCR) technologies, including repertoire analyses and engineering, are increasingly important in the clinical management of cellular immunity cancer, transplantation, other immune diseases. However, sensitive reliable methods for TCR cloning still lacking. Here, we report on SEQTR, a high-throughput approach to analyze human mouse repertoires that is more sensitive, reproducible, accurate as compared with commonly used assays, thus reliably captures complexity blood tumor...
Abstract A central challenge in developing personalized cancer cell immunotherapy is the identification of tumor-reactive T receptors (TCRs). By exploiting distinct transcriptomic profile cells relative to bystander cells, we build and benchmark TRTpred, an antigen-agnostic silico predictor TCRs. We integrate TRTpred with avidity derive a combinatorial algorithm clinically relevant TCRs for therapy it patient-derived xenografts.
T cells are important for controlling ovarian cancer (OC). We previously demonstrated that combinatorial use of a personalized whole-tumor lysate-pulsed dendritic cell vaccine (OCDC), bevacizumab (Bev), and cyclophosphamide (Cy) elicited neoantigen-specific prolonged OC survival. Here, we hypothesize adding acetylsalicylic acid (ASA) low-dose interleukin (IL)-2 would increase the efficacy in recurrent advanced phase I trial (NCT01132014). By ASA IL-2 to OCDC-Bev-Cy regimen, vaccine-specific...
The accurate identification and prioritization of antigenic peptides is crucial for the development personalized cancer immunotherapies. Publicly available pipelines to predict clinical neoantigens do not allow direct integration mass spectrometry immunopeptidomics data, which can uncover derived from various canonical noncanonical sources. To address this, we present an end-to-end proteogenomic pipeline, called NeoDisc, that combines state-of-the-art publicly in-house software...
Abstract Approaches to analyze and cluster T‐cell receptor (TCR) repertoires reflect antigen specificity are critical for the diagnosis prognosis of immune‐related diseases development personalized therapies. Sequence‐based approaches showed success but remain restrictive, especially when amount experimental data used training is scarce. Structure‐based which represent powerful alternatives, notably optimize TCRs affinity toward specific epitopes, show limitations large‐scale predictions. To...
Loss of epithelial differentiation and extracellular matrix (ECM) remodeling are known to facilitate cancer progression associated with poor prognosis in patients lung cancer. We have identified Receptor-interacting serine/threonine protein kinase 4 (RIP4) as a regulator tumor adenocarcinoma (AC). Bioinformatics analyses human AC samples showed that poorly differentiated tumors express low levels RIP4, whereas high better overall survival. In vitro, cells expressing reduced RIP4 enhanced...
Abstract The profiles, specificity and dynamics of tumor-specific clonotypes that are associated with clinical response to adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) remain unclear. Using single-cell RNA/TCR-sequencing, we tracked TIL from baseline tumors ACT products post-ACT blood tumor samples in melanoma patients treated TIL-ACT. Patients responses had enriched tumor-reactive TILs, which were more effectively mobilized upon vitro expansion, yielding higher...
Personalized T-cell therapy is emerging as a pivotal treatment of cancer care by tailoring cellular therapies to individual genetic and antigenic profiles, echoing the exciting success personalized vaccines. We describe here parallel evolution analogies vaccines therapies.
Hypochlorous acid (HOCl)-treated whole tumor cell lysates (Ox-L) have been shown to be more immunogenic when used as an antigen source for therapeutic dendritic (DC)-based vaccines, improving downstream immune responses both in vitro and vivo. However, the mechanisms behind improved immunogenicity are still elusive. To address this question, we conducted a proteomic immunopeptidomics analyses map modifications alterations introduced by HOCl treatment using human melanoma line model system....
Abstract Approaches to analyse and cluster TCR repertoires reflect antigen specificity are critical for the diagnosis prognosis of immune-related diseases development personalized therapies. Sequence-based approaches showed success but remain restrictive, especially when amount experimental data used training is scarce. Structure-based which represent powerful alternatives, notably optimize TCRs affinity towards specific epitopes, show limitations large scale predictions. To handle these...
Abstract Adoptive cell therapy (ACT) using ex vivo expanded tumor-infiltrating T lymphocytes (TILs) can mediate responses in metastatic melanoma, but long-term efficacy remains limited to a fraction of patients. Here we interrogated tumor-microenvironment (TME) cellular states and interactions longitudinal samples from 13 melanoma patients treated with TIL-ACT our clinical study ( NCT03475134 ). We performed single-cell RNA-seq spatial proteomic analyses pre- post-ACT tumor tissues showed...
2533 Background: Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has demonstrated a curative potential for patients with metastatic melanoma (MM). Nevertheless, activity remains unsatisfactory in many patients, requiring development of biomarkers that predict therapeutic efficacy. We report results single-center phase I study to assess feasibility, safety and efficacy TIL-ACT MM (NCT03475134). Methods: Patients refractory at least one prior line received TIL...