Application of Monoclonal Antibody G250 Recognizing Carbonic Anhydrase IX in Renal Cell Carcinoma

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2013 Jun 14

PMID 23759990

Citations 36

Authors

Jeannette C Oosterwijk-Wakka

Otto C Boerman

Peter F A Mulders

Egbert Oosterwijk

Affiliations

Soon will be listed here.

Abstract

Monoclonal antibody G250 (mAbG250) recognizes a determinant on carbonic anhydrase IX (CAIX). CAIX is expressed by virtually all renal cell carcinomas of the clear cell type (ccRCC), but expression in normal tissues is restricted. The homogeneous CAIX expression in ccRCC and excellent targeting capability of mAbG250 in animal models led to the initiation of the clinical evaluation of mAbG250 in (metastatic) RCC (mRCC) patients. Clinical studies confirmed the outstanding targeting ability of mAbG250 and cG250 PET imaging, as diagnostic modality holds great promise for the future, both in detecting localized and advanced disease. Confirmation of the results obtained in the non-randomized clinical trials with unmodified cG250 is needed to substantiate the value of cG250 treatment in mRCC. cG250-Based radio immuno-therapy (RIT) holds promise for treatment of patients with small-volume disease, and adjuvant treatment with unmodified cG250 may be of value in selected cases. In the upcoming years, ongoing clinical trials should provide evidence for these assumptions. Lastly, whether cG250-based RIT can be combined with tyrosine kinase inhibitors, which constitutes the current standard treatment for mRCC, needs to be established.

Citing Articles

Retrospective study assessing the role of the androgen receptor in clear cell renal cell cancer patients treated with VEGFR inhibitors in monotherapy.

Osorio L, Grazioso T, de Velasco G, Etxaniz O, Perez-Gracia J, Pinto A Clin Transl Oncol. 2024; .

PMID: 39365364 DOI: 10.1007/s12094-024-03652-9.

Combined UTMD-Nanoplatform for the Effective Delivery of Drugs to Treat Renal Cell Carcinoma.

Dai T, Wang Q, Zhu L, Luo Q, Yang J, Meng X Int J Nanomedicine. 2024; 19:8519-8540.

PMID: 39185349 PMC: 11345023. DOI: 10.2147/IJN.S459960.

Tumor targeted alpha particle therapy with an actinium-225 labelled antibody for carbonic anhydrase IX.

Morgan K, Wichmann C, Osellame L, Cao Z, Guo N, Scott A Chem Sci. 2024; 15(9):3372-3381.

PMID: 38425522 PMC: 10901495. DOI: 10.1039/d3sc06365h.

Emerging Immunotherapy Approaches for Advanced Clear Cell Renal Cell Carcinoma.

Meng L, Collier K, Wang P, Li Z, Monk P, Mortazavi A Cells. 2024; 13(1).

PMID: 38201238 PMC: 10777977. DOI: 10.3390/cells13010034.

The co-delivery of adenovirus-based immune checkpoint vaccine elicits a potent anti-tumor effect in renal carcinoma.

Jiang N, Zheng Y, Ding J, Wang J, Zhu F, Wang M NPJ Vaccines. 2023; 8(1):109.

PMID: 37542081 PMC: 10403580. DOI: 10.1038/s41541-023-00706-x.

References

Genega E, Ghebremichael M, Najarian R, Fu Y, Wang Y, Argani P . Carbonic anhydrase IX expression in renal neoplasms: correlation with tumor type and grade. Am J Clin Pathol. 2010; 134(6):873-9. PMC: 3778911. DOI: 10.1309/AJCPPPR57HNJMSLZ. View

Smith I, Procter M, Gelber R, Guillaume S, Feyereislova A, Dowsett M . 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007; 369(9555):29-36. DOI: 10.1016/S0140-6736(07)60028-2. View

Durrbach A, Angevin E, Poncet P, Rouleau M, Chavanel G, Chapel A . Antibody-mediated endocytosis of G250 tumor-associated antigen allows targeted gene transfer to human renal cell carcinoma in vitro. Cancer Gene Ther. 1999; 6(6):564-71. DOI: 10.1038/sj.cgt.7700085. View

Divgi C, Pandit-Taskar N, Jungbluth A, Reuter V, Gonen M, Ruan S . Preoperative characterisation of clear-cell renal carcinoma using iodine-124-labelled antibody chimeric G250 (124I-cG250) and PET in patients with renal masses: a phase I trial. Lancet Oncol. 2007; 8(4):304-10. DOI: 10.1016/S1470-2045(07)70044-X. View

Steffens M, Boerman O, Oosterwijk-Wakka J, Oosterhof G, Witjes J, Koenders E . Targeting of renal cell carcinoma with iodine-131-labeled chimeric monoclonal antibody G250. J Clin Oncol. 1997; 15(4):1529-37. DOI: 10.1200/JCO.1997.15.4.1529. View

Jaakkola P, Mole D, Tian Y, Wilson M, Gielbert J, Gaskell S . Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science. 2001; 292(5516):468-72. DOI: 10.1126/science.1059796. View

Rixe O, Bukowski R, Michaelson M, Wilding G, Hudes G, Bolte O . Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study. Lancet Oncol. 2007; 8(11):975-84. DOI: 10.1016/S1470-2045(07)70285-1. View

Bui M, Visapaa H, Seligson D, Kim H, Han K, Huang Y . Prognostic value of carbonic anhydrase IX and KI67 as predictors of survival for renal clear cell carcinoma. J Urol. 2004; 171(6 Pt 1):2461-6. DOI: 10.1097/01.ju.0000116444.08690.e2. View

Poeppel T, Krause B, Heusner T, Boy C, Bockisch A, Antoch G . PET/CT for the staging and follow-up of patients with malignancies. Eur J Radiol. 2009; 70(3):382-92. DOI: 10.1016/j.ejrad.2009.03.051. View

10.

Surfus J, Hank J, Oosterwijk E, Welt S, Lindstrom M, Albertini M . Anti-renal-cell carcinoma chimeric antibody G250 facilitates antibody-dependent cellular cytotoxicity with in vitro and in vivo interleukin-2-activated effectors. J Immunother Emphasis Tumor Immunol. 1996; 19(3):184-91. DOI: 10.1097/00002371-199605000-00003. View

11.

Siebels M, Rohrmann K, Oberneder R, Stahler M, Haseke N, Beck J . A clinical phase I/II trial with the monoclonal antibody cG250 (RENCAREX®) and interferon-alpha-2a in metastatic renal cell carcinoma patients. World J Urol. 2010; 29(1):121-6. DOI: 10.1007/s00345-010-0570-2. View

12.

Brouwers A, Frielink C, Oosterwijk E, Oyen W, Corstens F, Boerman O . Interferons can upregulate the expression of the tumor associated antigen G250-MN/CA IX, a potential target for (radio)immunotherapy of renal cell carcinoma. Cancer Biother Radiopharm. 2003; 18(4):539-47. DOI: 10.1089/108497803322287619. View

13.

Oosterwijk-Wakka J, Kats-Ugurlu G, Leenders W, Kiemeney L, Old L, Mulders P . Effect of tyrosine kinase inhibitor treatment of renal cell carcinoma on the accumulation of carbonic anhydrase IX-specific chimeric monoclonal antibody cG250. BJU Int. 2010; 107(1):118-25. DOI: 10.1111/j.1464-410X.2010.09314.x. View

14.

Bismar T, Bianco F, Zhang H, Li X, Sarkar F, Sakr W . Quantification of G250 mRNA expression in renal epithelial neoplasms by real-time reverse transcription-PCR of dissected tissue from paraffin sections. Pathology. 2003; 35(6):513-7. DOI: 10.1080/00313020310001619910. View

15.

Potter C, Harris A . Hypoxia inducible carbonic anhydrase IX, marker of tumour hypoxia, survival pathway and therapy target. Cell Cycle. 2004; 3(2):164-7. View

16.

Divgi C, Uzzo R, Gatsonis C, Bartz R, Treutner S, Yu J . Positron emission tomography/computed tomography identification of clear cell renal cell carcinoma: results from the REDECT trial. J Clin Oncol. 2012; 31(2):187-94. PMC: 5795663. DOI: 10.1200/JCO.2011.41.2445. View

17.

Sternberg C, Davis I, Mardiak J, Szczylik C, Lee E, Wagstaff J . Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010; 28(6):1061-8. DOI: 10.1200/JCO.2009.23.9764. View

18.

Atkins M, Regan M, McDermott D, Mier J, Stanbridge E, Youmans A . Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer. Clin Cancer Res. 2005; 11(10):3714-21. DOI: 10.1158/1078-0432.CCR-04-2019. View

19.

Davis I, Liu Z, Saunders W, Lee F, Spirkoska V, Hopkins W . A pilot study of monoclonal antibody cG250 and low dose subcutaneous IL-2 in patients with advanced renal cell carcinoma. Cancer Immun. 2007; 7:14. PMC: 2935743. View

20.

Patard J, Pignot G, Escudier B, Eisen T, Bex A, Sternberg C . ICUD-EAU International Consultation on Kidney Cancer 2010: treatment of metastatic disease. Eur Urol. 2011; 60(4):684-90. DOI: 10.1016/j.eururo.2011.06.017. View