Pretargeted Radioimmunotherapy of Prostate Cancer with an Anti-TROP-2xAnti-HSG Bispecific Antibody and a 177Lu-Labeled Peptide

被引:24
作者
van Rij, Catharina M. [1 ,2 ]
Frielink, Cathelijne [1 ]
Goldenberg, David M. [3 ,4 ]
Sharkey, Robert M. [3 ]
Lutje, Susanne [1 ]
McBride, William J. [3 ]
Oyen, Wim J. G. [1 ]
Boerman, Otto C. [1 ]
机构
[1] Radboud Univ Nijmegen, Dept Radiol & Nucl Med, Med Ctr, NL-6525 GA Nijmegen, Netherlands
[2] Radboud Univ Nijmegen, Dept Clin Pharm, Med Ctr, NL-6525 GA Nijmegen, Netherlands
[3] Immunomedics Inc, Morris Plains, NJ USA
[4] Garden State Canc Ctr, Ctr Mol Immunol, Morris Plains, NJ USA
关键词
TROP-2; prostate cancer; pretargeted radioimmunotherapy; bispecific monoclonal antibody; MONOCLONAL-ANTIBODY; HAPTEN-PEPTIDE; IMMUNO-PET; RADIONUCLIDE; CARCINOMA; RS7-3G11;
D O I
10.1089/cbr.2014.1660
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
TROP-2 is a pancarcinoma marker that is expressed at high levels in many epithelial cancers, including prostate cancer (PC). The trivalent bispecific antibody TF12 (anti-TROP2xanti-HSG [histamine-succinyl-glycine]) has shown to effectively target PC. In this study, the efficacy of pretargeted radioimmunotherapy (PRIT) with multiple cycles of TF12 and Lu-177-labeled diHSG-peptide (IMP288) in mice with s.c. PC3 tumors was investigated and compared with that of conventional RIT with Lu-177-labeled anti-TROP-2 mAb hRS7. Methods: The potential of one, two, and three cycles of PRIT using the TF12 pretargeted Lu-177-IMP288 (41 MBq per cycle) was determined in mice with s.c. PC3 tumors, and compared with the efficacy and toxicity of RIT with Lu-177-hRS7 dosed at the maximum tolerated dose (11 MBq). Results: PRIT of two and three cycles showed significantly higher median survival (>150 days) compared with PRIT of one cycle of TF12 and Lu-177-IMP288 (111 days, p<0.001) or the controls (76 days, p<0.0001). All mice treated with the mAb Lu-177-hRS7 survived at the end of the experiment (150 days), compared with 80% in the mice that were treated with three cycles of PRIT and 70% in the group that received two cycles of PRIT. Clinically significant hematologic toxicity was found only in the groups that received either three cycles of PRIT (p<0.0009) or RIT (p<0.0001). Conclusions: TROP-2-expressing PC can be targeted efficiently with TF12 and radiolabeled IMP288. Lu-177-IMP288 accumulated rapidly in the tumors. PRIT of multiple cycles inhibited the growth of s.c. PC3 tumors. Clinically relevant hematological toxicity was observed in the group that received three cycles of PRIT; however, conventional RIT with the parent mAb Lu-177-hRS7 was at least as effective with similar toxicity.
引用
收藏
页码:323 / 329
页数:7
相关论文
共 16 条
[11]   Pretargeting: taking an alternate route for localizing radionuclides [J].
Sharkey, Robert M. ;
Chang, Chien-Hsing ;
Rossi, Edmund A. ;
McBride, William J. ;
Goldenberg, David M. .
TUMOR BIOLOGY, 2012, 33 (03) :591-600
[12]   SPECIFICITY AND PROPERTIES OF MAB RS7-3G11 AND THE ANTIGEN DEFINED BY THIS PANCARCINOMA MONOCLONAL-ANTIBODY [J].
STEIN, R ;
BASU, A ;
CHEN, S ;
SHIH, LB ;
GOLDENBERG, DM .
INTERNATIONAL JOURNAL OF CANCER, 1993, 55 (06) :938-946
[13]   Phase II Study of Lutetium-177-Labeled Anti-Prostate-Specific Membrane Antigen Monoclonal Antibody J591 for Metastatic Castration-Resistant Prostate Cancer [J].
Tagawa, Scott T. ;
Milowsky, Matthew I. ;
Morris, Michael ;
Vallabhajosula, Shankar ;
Christos, Paul ;
Akhtar, Naveed H. ;
Osborne, Joseph ;
Goldsmith, Stanley J. ;
Larson, Steve ;
Taskar, Neeta Pandit ;
Scher, Howard I. ;
Bander, Neil H. ;
Nanus, David M. .
CLINICAL CANCER RESEARCH, 2013, 19 (18) :5182-5191
[14]   Anti-Prostate-Specific Membrane Antigen-Based Radioimmunotherapy for Prostate Cancer [J].
Tagawa, Scott T. ;
Beltran, Himisha ;
Vallabhajosula, Shankar ;
Goldsmith, Stanley J. ;
Osborne, Joseph ;
Matulich, Dan ;
Petrillo, Kristen ;
Parmar, Sarojben ;
Nanus, David M. ;
Bander, Neil H. .
CANCER, 2010, 116 (04) :1075-1083
[15]   Pretargeted immuno-PET and radioimmunotherapy of prostate cancer with an anti-TROP-2 x anti-HSG bispecific antibody [J].
van Rij, Catharina M. ;
Lutje, Susanne ;
Frielink, Cathelijne ;
Sharkey, Robert M. ;
Goldenberg, David M. ;
Franssen, Gerben M. ;
McBride, William J. ;
Rossi, Edmund A. ;
Oyen, Wim J. G. ;
Boerman, Otto C. .
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 2013, 40 (09) :1377-1383
[16]   Imaging of Prostate Cancer with Immuno-PET and Immuno-SPECT Using a Radiolabeled Anti-EGP-1 Monoclonal Antibody [J].
van Rij, Catharina M. ;
Sharkey, Robert M. ;
Goldenberg, David M. ;
Frielink, Cathelijne ;
Molkenboer, Janneke D. M. ;
Franssen, Gerben M. ;
van Weerden, Wietske M. ;
Oyen, Wim J. G. ;
Boerman, Otto C. .
JOURNAL OF NUCLEAR MEDICINE, 2011, 52 (10) :1601-1607