BACKGROUND: Monoclonal antibodies (MAbs) are used for targeting agents to tumours while minimizing normal tissue exposure. METHODS: A new anti-prostate cancer MAb, BLCA-38, was radioiodinated (I125) and assessed for its ability to target subcutaneous human prostate cancer (DU-145) xenografts after systemic intraperitoneal administration. For comparison, the profile of J591 MAb (now in clinical trial) against LNCaP-LN3 tumours was examined. Biodistribution profiles were obtained at various times, by assessing injected dose/gram (%ID/g) and xenograft to blood (X/B) ratios. Microautoradiography of xenografts was performed. After conjugation with a melittin peptide toxin, the profiles of BLCA-38 and J591 were compared with that of an irrelevant antibody, DS-1. RESULTS: Xenograft localization by 125I-labeled BLCA-38 and J591 MAbs to their relevant antigen-positive tumors was comparable, and there was no unusual localization in nontumour tissues. F(ab')2 and Fab fragments gave improved X/B ratios, but the %ID/g xenograft was decreased and they accumulated in kidneys, bladder and stomach. In contrast, the conjugates of irrelevant antibody showed no tumour targeting. Microautoradiography showed more tumour accumulation of MAbs than F(ab')2s or Fabs. CONCLUSIONS: BLCA-38 can target prostate cancer in vivo almost as effectively as J591. Given that J591 is used clinically, BLCA-38, which targets a different antigen, has potential for radioimmunoscintigraphy and for therapeutic targeting of prostate cancer.
BACKGROUND: Monoclonal antibodies (MAbs) are used for targeting agents to tumours while minimizing normal tissue exposure. METHODS: A new anti-prostate cancer MAb, BLCA-38, was radioiodinated (I125) and assessed for its ability to target subcutaneous humanprostate cancer (DU-145) xenografts after systemic intraperitoneal administration. For comparison, the profile of J591 MAb (now in clinical trial) against LNCaP-LN3 tumours was examined. Biodistribution profiles were obtained at various times, by assessing injected dose/gram (%ID/g) and xenograft to blood (X/B) ratios. Microautoradiography of xenografts was performed. After conjugation with a melittin peptide toxin, the profiles of BLCA-38 and J591 were compared with that of an irrelevant antibody, DS-1. RESULTS: Xenograft localization by 125I-labeled BLCA-38 and J591 MAbs to their relevant antigen-positive tumors was comparable, and there was no unusual localization in nontumour tissues. F(ab')2 and Fab fragments gave improved X/B ratios, but the %ID/g xenograft was decreased and they accumulated in kidneys, bladder and stomach. In contrast, the conjugates of irrelevant antibody showed no tumour targeting. Microautoradiography showed more tumour accumulation of MAbs than F(ab')2s or Fabs. CONCLUSIONS: BLCA-38 can target prostate cancer in vivo almost as effectively as J591. Given that J591 is used clinically, BLCA-38, which targets a different antigen, has potential for radioimmunoscintigraphy and for therapeutic targeting of prostate cancer.
Authors: Jeffrey V Leyton; Tove Olafsen; Mark A Sherman; Karl B Bauer; Patrick Aghajanian; Robert E Reiter; Anna M Wu Journal: Protein Eng Des Sel Date: 2008-10-28 Impact factor: 1.650
Authors: Jeffrey V Leyton; Tove Olafsen; Eric J Lepin; Scott Hahm; Karl B Bauer; Robert E Reiter; Anna M Wu Journal: Clin Cancer Res Date: 2008-11-15 Impact factor: 12.531
Authors: Yu Shi; Bingyang Shi; Arun V Everest Dass; Yiqing Lu; Nima Sayyadi; Liisa Kautto; Robert D Willows; Roger Chung; James Piper; Helena Nevalainen; Bradley Walsh; Dayong Jin; Nicolle H Packer Journal: Sci Rep Date: 2016-11-22 Impact factor: 4.379
Authors: Dhanusha Sabanathan; Douglas H Campbell; Vicki M Velonas; Sandra Wissmueller; Hubert Mazure; Marko Trifunovic; Pirooz Poursoltan; Kevin Ho Shon; Tiffany R Mackay; Maria E Lund; Yanling Lu; Paul J Roach; Dale L Bailey; Bradley J Walsh; David Gillatt; Howard Gurney Journal: Asia Ocean J Nucl Med Biol Date: 2021