Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 136, Issue 1, Pages 127-137Publisher
WILEY
DOI: 10.1002/ijc.28973
Keywords
thyroglobulin antibodies; immunotherapy; GVAX; CTLA-4
Categories
Funding
- NIH [DK080351, K23 CA148964-01, R21 (CA1266058)]
- Dutch Cancer Society (KFW) [VU 2006-3697]
- National Science Council, Taipei, Taiwan [NSC 101-2320-B-009-005, NSC 102-2628-B-009-002-MY2]
- NCI SPORE in Gastrointestinal Cancers [P50 CA062924]
- Universita degli Studi G.D'Annunzio, Chieti, Italy
- Prostate Cancer Foundation (PCF) Competitive Research Award
- Manpei Suzuki Diabetes Foundation
- American Society of Clinical Oncology Young Investigator Award
- Viragh Family Foundation
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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. = 553), prostate (No. = 535) or colon (No. = 58) cancer, before and after treatment with GVAX only (No. = 534), GVAX plus ipilimumab (No. = 542) or ipilimumab (No. = 520), 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.
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