Dataset Information

Gene expression profile at single cell level of cells from whole lung to assess MAGE-A4 expressing tumor alterations in tumor microenvironment

ABSTRACT: Melanoma Antigen-A4 (MAGE-A4) is a common cancer testis antigen expressed in human non-small cell lung cancer; however, whether and how it contributes to cancer initiation and progression has remained less clear. We engineered mice to express human MAGE-A4 specifically in Club cells of the bronchial epithelium, with or without loss of Pten in the same cells, to investigate the role of MAGE-A4 in tumor initiation and development. We used single cell transcriptomics and flow cytometry to evaluate the immune and other cells in the lung/lung tumor microenvironment that were altered in response to this cancer testis antigen. We found that endothelial cells in MAGE-A4 expression models upregulate CXCL12, which likely contributes to the increased plasma cell recruitment to the lungs infiltrating MAGE-A4-expressing lung tumors in both mouse and human. Single cells were isolated from whole lung of mice at 5 months of age when tumor had developed in MAG4/Pt lungs and were analyzed using scRNA-seq.

ORGANISM(S): Mus musculus

PROVIDER: GSE267420 | GEO | 2025/02/19

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Afamitresgene autoleucel, an HLA-restricted autologous specific peptide enhanced affinity receptor (SPEAR) T-cell therapy targeting MAGE-A4, was developed to treat HLA-A*02 positive patients with MAGE-A4 expressing solid tumors. A multicenter, dose-escalation, Phase 1 trial (NCT03132922) was conducted evaluating afamitresgene autoleucel in patients with relapsed or refractory (≥1 prior line of therapy) metastatic solid tumors. The primary endpoint was safety. The secondary endpoint was anti-tumor activity including overall response rate, best overall response, time to response, duration of response, duration of stable disease, progression-free survival and overall survival. Thirty-eight patients were treated with afamitresgene autoleucel across 9 tumor types, including 16 with synovial sarcoma (SS). Overall, afamitresgene autoleucel was well tolerated. The most common adverse events were cytopenias. Cytokine release syndrome occurred in 55% of all patients with severity grade ≤2 in 90% of reported cases. Overall response rate (ORR) was 24% and disease control rate (DCR) was 74% with objective responses in 7 patients with SS, 1 patient with non-small cell lung cancer, and 1 patient with head and neck squamous cell carcinoma. ORR in patients with SS, all prior treated with ifosfamide chemotherapy, was 44%, and DCR was 94%. Median progression-free survival and overall survival were 20.4 weeks (95% CI: 10.0, 52.1) and 58.1 weeks (95% CI: 36.3,-), respectively, for patients with SS and 12.3 weeks (95% CI: 10.857, 19.1) and 42.9 weeks (95% CI: 20.7, -), respectively, for the overall population. Translational findings demonstrated that afamitresgene autoleucel infiltrates into tumors, has an IFNγ-driven mechanism-of-action, and triggers adaptive immune responses. Overall, afamitresgene autoleucel has an acceptable safety profile with early and durable responses in HLA-A*02 positive patients with MAGE-A4 expressing solid tumors, especially in patients with metastatic SS. The recommended treatment regimen for Phase 2 evaluation involves lymphodepleting chemotherapy consisting of cyclophosphamide 600 mg/m2 x 3 days and fludarabine 30 mg/m2 x 4 days followed by afamitresgene autoleucel at a dose range of 1 to 10 billion transduced T-cells.

Dataset Information

Gene expression profile at single cell level of cells from whole lung to assess MAGE-A4 expressing tumor alterations in tumor microenvironment

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets