Clinical protocol phase II study of tumor infiltrating lymphocytes in advanced tumors with alterations in the SWI/SNF complex: the TILTS study

Future Oncol. 2024;20(32):2437-2445. doi: 10.1080/14796694.2024.2385287. Epub 2024 Aug 12.

Abstract

The SWI/SNF complex is a chromatin remodeling complex comprised by several proteins such as SMARCA4 or SMARCB1. Mutations in its components can lead to the development of aggressive rhabdoid tumors such as epithelioid sarcoma, malignant rhabdoid tumor or small cell carcinoma of the ovary hypercalcemic type, among others. These malignancies tend to affect young patients and their prognosis is poor given the lack of effective treatments. Characteristically, these tumors are highly infiltrated by TILs, suggesting that some lymphocytes are recognizing tumor antigens. The use of those TILs as a therapeutic strategy is a promising approach worth exploring. Here, we report the clinical protocol of the TILTS study, a Phase II clinical trial assessing personalized adoptive cell therapy with TILs in patients affected by these tumor types.Clinical Trial Registration: 2023-504632-17-00 (www.clinicaltrialsregister.eu) (ClinicalTrials.gov).

Keywords: SMARCA4; SMARCB1; SWI/SNF complex; TILTS; TILs; adoptive cell therapy; immunotherapy; rhabdoid tumors.

Plain language summary

[Box: see text].

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial Protocol

MeSH terms

  • Adult
  • Chromosomal Proteins, Non-Histone / genetics
  • Clinical Trials, Phase II as Topic
  • DNA Helicases / genetics
  • Female
  • Humans
  • Immunotherapy, Adoptive / methods
  • Lymphocytes, Tumor-Infiltrating* / immunology
  • Lymphocytes, Tumor-Infiltrating* / metabolism
  • Male
  • Mutation
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Rhabdoid Tumor / genetics
  • Rhabdoid Tumor / pathology
  • Rhabdoid Tumor / therapy
  • SMARCB1 Protein* / genetics
  • SMARCB1 Protein* / metabolism
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism

Substances

  • SMARCA4 protein, human
  • SMARCB1 Protein
  • Transcription Factors
  • SMARCB1 protein, human
  • Nuclear Proteins
  • DNA Helicases
  • Chromosomal Proteins, Non-Histone