Pilot Trial of FANG Immunotherapy in Ewing's Sarcoma.
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.
Mary Crowley Cancer Research Centers, Dallas, Texas, USA; Texas Oncology, P.A., Dallas, Texas, USA; Medical City Dallas Hospital, Dallas, Texas, USA.
Maurizio
M
Ghisoli
Mary Crowley Cancer Research Centers, Dallas, Texas, USA; Texas Oncology, P.A., Dallas, Texas, USA.
Minal
M
Barve
Mary Crowley Cancer Research Centers, Dallas, Texas, USA; Texas Oncology, P.A., Dallas, Texas, USA; Gradalis, Inc., Dallas, Texas, USA.
Reva
R
Schneider
Texas Oncology, P.A., Dallas, Texas, USA; Baylor University Medical Center, Dallas, Texas, USA.
Robert
R
Mennel
Texas Oncology, P.A., Dallas, Texas, USA; Medical City Dallas Hospital, Dallas, Texas, USA.
Carl
C
Lenarsky
Gradalis, Inc., Dallas, Texas, USA.
Gladice
G
Wallraven
Gradalis, Inc., Dallas, Texas, USA.
Beena O
BO
Pappen
Medical City Children's Hospital, Dallas, Texas, USA.
John
J
LaNoue
Gradalis, Inc., Dallas, Texas, USA.
Padmasini
P
Kumar
Mary Crowley Cancer Research Centers, Dallas, Texas, USA.
Derek
D
Nemunaitis
Mary Crowley Cancer Research Centers, Dallas, Texas, USA.
Alyssa
A
Roth
Mary Crowley Cancer Research Centers, Dallas, Texas, USA.
James
J
Nemunaitis
Gradalis, Inc., Dallas, Texas, USA.
Sam
S
Whiting
Mary Crowley Cancer Research Centers, Dallas, Texas, USA; Gradalis, Inc., Dallas, Texas, USA.
Neil
N
Senzer
Gradalis, Inc., Dallas, Texas, USA.
Frederick A
FA
Fletcher
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.
John
J
Nemunaitis
D000293:Adolescent; D000328:Adult; D005260:Female; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000628:therapy; D010865:Pilot Projects; D012512:Sarcoma, Ewing / Q000628:therapy*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor