Development of thyroglobulin antibodies after GVAX immunotherapy is associated with prolonged survival.
Cancer immunotherapy induces a variety of autoinflammatory responses, including those against the thyroid gland, which can be exploited to predict clinical outcomes. Considering the paucity of information about thyroid autoimmunity in patients receiving cancer vaccines, we designed our study to assess the development of thyroglobulin antibodies (TgAbs) in patients treated with GVAX (vaccine made of a tumor cell type transfected with GM-CSF) and/or ipilimumab and correlated seroconversion with survival. Using both in house and commercial ELISA assays, we measured TgAbs in patients with pancreatic (No. = 53), prostate (No. = 35) or colon (No. = 8) cancer, before and after treatment with GVAX only (No. = 34), GVAX plus ipilimumab (No. = 42) or ipilimumab (No. = 20), and correlated their levels with patient's survival, disease status and T-cell surface markers. Antibodies to thyroperoxidase, myeloperoxidase, proteinase 3, insulin and actin were also measured. TgAbs specifically developed after GVAX, independent of the underlying cancer (81% in prostate, 75% colon cancer and 76% pancreatic cancer) and co-administration of ipilimumab (75% in GVAX only and 78% in GVAX plus ipilimumab). This TgAbs seroconversion could be detected mainly by the in house assay, suggesting that the thyroglobulin epitopes recognized by the antibodies induced by GVAX are different from the epitopes seen in the classic form of Hashimoto thyroiditis. Notably, TgAbs seroconversion was associated with significantly prolonged survival (p = 0.01 for pancreas and p = 0.005 for prostate cancer). In conclusion, GVAX immunotherapy induces the appearance of TgAbs that recognize a unique antigenic repertoire and associate with prolonged survival.
Department of Pathology, Johns Hopkins University, Baltimore, MD.
Alessandra
A
De Remigis
Tanja D
TD
de Gruijl
Jennifer N
JN
Uram
Schey-Cherng
SC
Tzou
Shintaro
S
Iwama
Monica V
MV
Talor
Todd D
TD
Armstrong
Saskia J A M
SJ
Santegoets
Susan F
SF
Slovin
Lei
L
Zheng
Daniel A
DA
Laheru
Elizabeth M
EM
Jaffee
Winald R
WR
Gerritsen
Alfons J M
AJ
van den Eertwegh
Dung T
DT
Le
Patrizio
P
Caturegli
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000912:Antibodies, Neoplasm / Q000097:blood; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001323:Autoantibodies / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D045744:Cell Line, Tumor; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000097:blood / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D003131:Combined Modality Therapy; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D010190:Pancreatic Neoplasms / Q000097:blood / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D013954:Thyroglobulin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood; D014611:Vaccination
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D001323:Autoantibodies; D019496:Cancer Vaccines; C000593794:GVAX vaccine; D000074324:Ipilimumab; D012333:RNA, Messenger; D013972:Thyrotropin; D013954:Thyroglobulin
CTLA-4; GVAX; immunotherapy; thyroglobulin antibodies