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Mol Ther. 2015 Jun;23(6):1103-1109. doi: 10.1038/mt.2015.43. Epub 2015 Mar 19.

Pilot Trial of FANG Immunotherapy in Ewing's Sarcoma.

Author information

1
Mary Crowley Cancer Research Centers, Dallas, Texas, USA; Texas Oncology, P.A., Dallas, Texas, USA; Medical City Dallas Hospital, Dallas, Texas, USA.
2
Mary Crowley Cancer Research Centers, Dallas, Texas, USA; Texas Oncology, P.A., Dallas, Texas, USA.
3
Mary Crowley Cancer Research Centers, Dallas, Texas, USA; Texas Oncology, P.A., Dallas, Texas, USA; Gradalis, Inc., Dallas, Texas, USA.
4
Texas Oncology, P.A., Dallas, Texas, USA; Baylor University Medical Center, Dallas, Texas, USA.
5
Texas Oncology, P.A., Dallas, Texas, USA; Medical City Dallas Hospital, Dallas, Texas, USA.
6
Gradalis, Inc., Dallas, Texas, USA.
7
Medical City Children's Hospital, Dallas, Texas, USA.
8
Mary Crowley Cancer Research Centers, Dallas, Texas, USA.
9
Mary Crowley Cancer Research Centers, Dallas, Texas, USA; Gradalis, Inc., Dallas, Texas, USA.
10
Mary Crowley Cancer Research Centers, Dallas, Texas, USA; Texas Oncology, P.A., Dallas, Texas, USA; Gradalis, Inc., Dallas, Texas, USA; Medical City Dallas Hospital, Dallas, Texas, USA. Electronic address: jnemunaitis@marycrowley.org.

Abstract

We report on 12 consecutive patients with advanced/metastatic Ewing's sarcoma who were treated as a separate cohort of a phase 1 trial of FANG autologous immunotherapy (1 × 10(6)-2.5 × 10(7) cells/intradermal injection each month for minimum 4 months). Safety and clinical response were monitored. Patient immune response to unmodified autologous tumor cells was assessed by gamma interferon-enzyme-linked immunospot (γIFN-ELISPOT) assay using peripheral blood mononuclear cells from baseline (pretreatment) and multiple postvaccination time points. None of the 12 patients (47 vaccinations) developed grade 2/3/4 drug-related toxicity. Median product release granulocyte-macrophage colony-stimulating factor expression was 1,941 pg/10(6) cells, and TGFβ1and TGFβ2 knockdown were 99 and 100%, respectively. Eight patients were assessed for ELISPOT response to autologous tumor cells at baseline and all (100%) were negative. In contrast, follow-up ELISPOT response at month 1 or month 4 (one patient) after FANG was positive in all eight patients. One patient achieved a partial tumor response (38% tumor reduction, RECIST 1.1). The Kaplan-Meier estimated survival of these 12 patients at 1 year was 75%. In this phase 1 study in patients with Ewing's sarcoma, FANG immunotherapy was well tolerated, elicited a tumor-specific systemic immune response in all patients, and was associated with favorable 1-year survival. Further clinical testing is indicated.

PMID:
25917459
PMCID:
PMC4817748
DOI:
10.1038/mt.2015.43
[Indexed for MEDLINE]
Free PMC Article

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