Publication Date
6-1-2024
Journal
Nature Cancer
DOI
10.1038/s43018-024-00749-6
PMID
38658775
PMCID
PMC11588040
PubMedCentral® Posted Date
12-1-2024
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Humans, Sarcoma, Middle Aged, Female, Male, Receptor, ErbB-2, Adult, Immunotherapy, Adoptive, Aged, Receptors, Chimeric Antigen, T-Lymphocytes, Lymphocyte Depletion, Prospective Studies, Vidarabine, Cyclophosphamide, Treatment Outcome
Abstract
In this prospective, interventional phase I study (NCT00902044) for patients with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T-cells (HER2-CART) after lymphodepletion with cyclophosphamide (Cy) +/− fludarabine (Flu): 1×108 T-cells/m2 after Flu (cohort A) or Flu/Cy (cohort B), and 1×108 CAR-positive T-cells/m2 after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2-CART after lymphodepletion. The determination of antitumor responses was the secondary outcome. Thirteen patients were treated in 14 enrollments with 7 receiving multiple infusions. HER2-CART expanded after 19 of 21 infusions. Nine of 12 patients in cohorts A and B developed grade 1–2 cytokine release syndrome (CRS). Two patients in cohort C experienced dose limiting toxicity with grade 3–4 CRS. Antitumor activity was observed with clinical benefit in 50% of patients treated. Tumor samples analyzed showed spatial heterogeneity of immune cells and clustering by sarcoma type and treatment response. Our results affirm HER2 as a CART target and demonstrate the safety of this therapeutic approach in sarcoma.
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