Hormonal and biochemical normalization and tumor shrinkage induced by anti-parathyroid hormone immunotherapy in a patient with metastatic parathyroid carcinoma

被引:70
作者
Betea, D
Bradwell, AR
Harvey, TC
Mead, GP
Schmidt-Gayk, H
Ghaye, B
Daly, AF
Beckers, A
机构
[1] Ctr Hosp Univ Sart Tilman, Dept Endocrinol, B-4000 Liege, Belgium
[2] Ctr Hosp Univ Sart Tilman, Dept Radiol, B-4000 Liege, Belgium
[3] Univ Birmingham, Dept Immunol, Sch Med, Birmingham B15 2TT, W Midlands, England
[4] Walsall Manor Hosp, Dept Med, Walsall WS2 9PS, W Midlands, England
[5] Heidelberg Univ, Dept Immunol, D-69120 Heidelberg, Germany
关键词
D O I
10.1210/jc.2003-031911
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
Parathyroid carcinoma is a rare cause of primary hyperparathyroidism, and the efficacy of medical therapy and chemo- and radiotherapy is poor in recurrent or metastatic disease. We report the first case of PTH immunization in which tumor shrinkage accompanied hormonal, biochemical, and clinical improvements in a patient with metastatic parathyroid carcinoma. A 50-yr-old woman with refractory parathyroid carcinoma and pulmonary metastases was immunized eight times between February 2001 and December 2003 with bovine and modified human PTH fragments and intact human PTH, mixed with Freund's adjuvant. Total and ionized calcium and PTH levels were assayed weekly for 6 months and regularly thereafter. Thoracic computed tomography scans were performed regularly. Antibodies to all PTH fragments were detected after two immunizations. Baseline PTH and total calcium were 213.0 ng/liter and 13.96 mg/dl, respectively, and remained elevated during the first three immunizations. From the fourth immunization onward, PTH and calcium decreased, and the patient's clinical condition improved markedly. PTH and calcium levels have remained controlled for more than 24 months, and the sizes (surface area) of pulmonary metastases decreased from baseline by 39-71%. This is the first evidence that PTH immunization not only can improve clinical, hormonal, and biochemical measures in parathyroid carcinoma but also has an antitumor effect.
引用
收藏
页码:3413 / 3420
页数:8
相关论文
共 25 条
[1]
Stimulation of autologous antitumor T-cell responses against medullary thyroid carcinoma using tumor lysate-pulsed dendritic cells [J].
Bachleitner-Hofmann, T ;
Stift, A ;
Friedl, J ;
Pfragner, R ;
Radelbauer, K ;
Dubsky, P ;
Schüller, G ;
Benkö, T ;
Niederle, B ;
Brostjan, C ;
Jakesz, R ;
Gnant, M .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2002, 87 (03) :1098-1104
[2]
Control of hypercalcaemia of parathyroid carcinoma by immunisation [J].
Bradwell, AR ;
Harvey, TC .
LANCET, 1999, 353 (9150) :370-373
[3]
Parathyroid hormone potentiates nucleotide-induced [Ca2+]i release in rat osteoblasts independently of Gq activation or cyclic monophosphate accumulation -: A mechanism for localizing systemic responses in bone [J].
Buckley, KA ;
Wagstaff, SC ;
McKay, G ;
Gaw, A ;
Hipskind, RA ;
Bilbe, G ;
Gallagher, JA ;
Bowler, WB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (12) :9565-9571
[4]
HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome [J].
Carpten, JD ;
Robbins, CM ;
Villablanca, A ;
Forsberg, L ;
Presciuttini, S ;
Bailey-Wilson, J ;
Simonds, WF ;
Gillanders, EM ;
Kennedy, AM ;
Chen, JD ;
Agarwal, SK ;
Sood, R ;
Jones, MP ;
Moses, TY ;
Haven, C ;
Petillo, D ;
Leotlela, PD ;
Harding, B ;
Cameron, D ;
Pannett, AA ;
Höög, A ;
Heath, H ;
James-Newton, LA ;
Robinson, B ;
Zarbo, RJ ;
Cavaco, BM ;
Wassif, W ;
Perrier, ND ;
Rosen, IB ;
Kristoffersson, U ;
Turnpenny, PD ;
Farnebo, LO ;
Besser, GM ;
Jackson, CE ;
Morreau, H ;
Trent, JM ;
Thakker, RV ;
Marx, SJ ;
Teh, BT ;
Larsson, C ;
Hobbs, MR .
NATURE GENETICS, 2002, 32 (04) :676-680
[5]
Treatment of hypercalcemia secondary to parathyroid carcinoma with a novel calcimimetic agent [J].
Collins, MT ;
Skarulis, MC ;
Bilezikian, JP ;
Silverberg, SJ ;
Spiegel, AM ;
Marx, SJ .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1998, 83 (04) :1083-1088
[6]
Cancer immunoediting: from immunosurveillance to tumor escape [J].
Dunn, GP ;
Bruce, AT ;
Ikeda, H ;
Old, LJ ;
Schreiber, RD .
NATURE IMMUNOLOGY, 2002, 3 (11) :991-998
[7]
HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours [J].
Howell, VM ;
Haven, CJ ;
Kahnoski, K ;
Khoo, SK ;
Petillo, D ;
Chen, J ;
Fleuren, GJ ;
Robinson, BG ;
Delbridge, LW ;
Philips, J ;
Nelson, AE ;
Krause, U ;
Hammje, K ;
Dralle, H ;
Hoang-Vu, C ;
Gimm, O ;
Marsh, DJ ;
Morreau, H ;
Teh, BT .
JOURNAL OF MEDICAL GENETICS, 2003, 40 (09) :657-663
[8]
Parathyroid carcinoma. [J].
Kebebew E. .
Current Treatment Options in Oncology, 2001, 2 (4) :347-354
[9]
Localization and reoperation results for persistent and recurrent parathyroid carcinoma [J].
Kebebew, E ;
Arici, C ;
Duh, JY ;
Clark, OH .
ARCHIVES OF SURGERY, 2001, 136 (08) :878-883
[10]
Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals [J].
Khan, N ;
Shariff, N ;
Cobbold, M ;
Bruton, R ;
Ainsworth, JA ;
Sinclair, AJ ;
Nayak, L ;
Moss, PAH .
JOURNAL OF IMMUNOLOGY, 2002, 169 (04) :1984-1992