Abstract
Background Adoptive cellular therapy (ACT) is a promising treatment for synovial sarcoma (SS) with reported response rates of over 50%. However, more work is needed to obtain deeper and more durable responses. SS has a â € cold' tumor immune microenvironment with low levels of major histocompatibility complex (MHC) expression and few T-cell infiltrates, which could represent a barrier toward successful treatment with ACT. We previously demonstrated that both MHC expression and T-cell infiltration can be increased using systemic interferon gamma (IFN-Î 3), which could improve the efficacy of ACT for SS. Case presentation We launched a phase I trial incorporating four weekly doses of IFN-γin an ACT regimen of high-dose cyclophosphamide (HD Cy), NY-ESO-1-specific T cells, and postinfusion low-dose interleukin (IL)-2. Two patients were treated. While one patient had significant tumor regression and resultant clinical benefit, the other patient suffered a fatal histiocytic myocarditis. Therefore, this cohort was terminated for safety concerns. Conclusion We describe a new and serious toxicity of immunotherapy from IFN-γcombined with HD Cy-based lymphodepletion and low-dose IL-2. While IFN-γshould not be used concurrently with HD Cy or with low dose IL-2, IFN-γmay still be important in sensitizing SS for ACT. Future studies should avoid using IFN-γduring the immediate period before/after cell infusion. Trial registration numbers NCT04177021, NCT01957709, and NCT03063632.
Original language | English (US) |
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Article number | e000247 |
Journal | Journal for immunotherapy of cancer |
Volume | 8 |
Issue number | 1 |
DOIs | |
State | Published - Apr 8 2020 |
Keywords
- CD8-positive T-lymphocytes
- immunotherapy, adoptive
- oncology
- sarcoma
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Molecular Medicine
- Oncology
- Pharmacology
- Cancer Research