Neutralizing antibodies and lymphocyte count as biomarkers in patients receiving oncolytic adenovirus TILT-123 and adoptive cell transfer of tumor-infiltrating lymphocytes for metastatic melanoma refractory to immune checkpoint inhibitors.
Rattachement africain : fi, dk, fr. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
9518 Background: Metastatic melanoma refractory to immune checkpoint inhibitors (ICI) remains a significant challenge. Adoptive Cell Transfer of Tumor-Infiltrating Lymphocytes (ACT-TILs) shows promise but can cause adverse events. Oncolytic adenovirus TILT-123 (igrelimogene litadenorepvec) coding for TNF and IL2 combined with ACT-TILs, offers an approach without conditioning therapies. We report long-term survival data from a phase I trial (TUNINTIL NCT04217473), and correlative clinical, histologic, and immunologic biomarker analyses. Methods: The aim was to evaluate safety of TILT-123 and ACT-TILs in patients with metastatic melanoma refractory to ICIs. Treatment was deemed safe and feasible. TILT-123 was given intravenously (IV) and intratumorally, ACT-TILs were given IV, without preconditioning chemotherapy or post-conditioning IL2. Five cohorts were completed in a 3+3 dose-incremental design without dose-limiting toxicities. Tumor biopsies were analyzed for adenoviral (Ad) genomes, PD-L1 expression and presence of CD4+ regulatory (reg), CD4+ and CD8+ T cells by multiplex immunofluorescence (mIF). TILT-123 DNA was quantified in tumors by qPCR, anti-Ad neutralizing antibodies (nAbs) analyzed in serum using luminescence titering assay. Disease control rate (DCR) was defined as Stable Disease or better using RECIST1.1, iRECIST, and PET criteria. Association of factors with survival and DCR was determined using Spearman’s rank correlation and multivariate analysis. Results: Patients varied in melanoma subtype (cutaneous n=8, mucosal n=5, uveal n=4), with a median age of 67 years (25-75 years). Following TILT-123 monotherapy, the DCR on D36 was 35% by RECIST 1.1 and iRECIST, and 63% by PET criteria. PET responses were seen in 31% of patients by D36. In the combination phase (D78) DCR per RECIST 1.1 or iRECIST was 38%, and 47% by PET criteria. Responses were seen in 27% of patients on D78 in PET, including a partial response lasting >8 months and a durable complete response in a mucosal melanoma patient. Median overall survival (mOS) was 447 days. Virus DNA was detected post-treatment in both injected and uninjected tumors. Patients with elevated titers of nAbs (by D22) showed a decrease in metabolism in non-injected lesions by day 36 (p=0.0101). Blood lymphocyte count decrease after TILT administration was associated with better DCR (p= 0.0188). mIF data showed patients achieving disease control had a higher percentage of intratumoral CD8+ T cells (p=0.037). Conclusions: ICI refractory melanoma patients receiving TILT-123 and ACT-TILs without preconditioning show signs of CD8+ T cell trafficking to the tumor microenvironment. nAbs and lymphocyte count decrease can be further investigated as biomarkers. Clinical trial information: NCT04217473 .
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Neutralizing antibodies and lymphocyte count as biomarkers in patients receiving oncolytic adenovirus TILT-123 and adoptive cell transfer of tumor-infiltrating lymphocytes for metastatic melanoma refractory to immune checkpoint inhibitors.
- Date Crossref
- 01/06/2025
- Éditeur
- American Society of Clinical Oncology (ASCO)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Biocenter Finland pays non établi dans la noticeStructure de recherche
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Copenhagen University Hospital Department of Oncology pays non établi dans la noticeÉtablissement de santé
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University of Helsinki Translational Immunology Research Program pays non établi dans la noticeUniversité ou école supérieure
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Helsinki University Hospital Department of Pathology pays non établi dans la noticeÉtablissement de santé
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Herlev Hospital pays non établi dans la noticeÉtablissement de santé
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Inserm pays non établi dans la noticeOrganisme public
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Nantes Université pays non établi dans la noticeUniversité ou école supérieure
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TILT Biotherapeutics Ltd. pays non établi dans la noticeEntreprise
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Cancer Gene Therapy Group pays non établi dans la noticeInstitution
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Nantes University Hospital Oncodermatology Department pays non établi dans la noticeUniversité ou école supérieure
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University of Nantes pays non établi dans la noticeUniversité ou école supérieure
Biocenter Finland, Department of Oncology — Copenhagen University Hospital et Translational Immunology Research Program — University of Helsinki, avec 8 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.