Phase I trial of iodine 131-labeled COL-1 in patients with gastrointestinal malignancies: influence of serum carcinoembryonic antigen and tumor bulk on pharmacokinetics.

Yu, Bo; Carrasquillo, Jorge A.; Milenic, Diane E.; Chung, Yang Jo; Perentesis, P.; Feuerestein, I; Eggensperger, Diane; Qi, Chen-F.; Paik, Chang H.; Reynolds, James C.; Grem, Jean L.; Curt, Gregory A.; Siler, Kathleen; Schlom, Jeffrey; Allegra, Carmen J.

doi:10.1200/jco.1996.14.6.1798

Cited by 28 publications

(27 citation statements)

References 25 publications

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“…In contrast, numerous studies performed with MoAbs directed against various epithelial tumors have only rarely shown partial or complete remissions (7)(8)(9)(10). This lack of antitumor effect is thought to be due to the limited radiation dose delivered together with the lower radiosensitivity of most epithelial tumors when compared with lymphomas.…”

Section: Introductionmentioning

confidence: 99%

Pretargeted α Emitting Radioimmunotherapy Using 213Bi 1,4,7,10-Tetraazacyclododecane-N,N′,N″,N‴-Tetraacetic Acid-Biotin

Yao¹,

Zhang²,

Garmestani³

et al. 2004

Clinical Cancer Research

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Purpose: The use of an ␣ emitter for radioimmunotherapy has potential advantages compared with ␤ emitters. When administered systemically optimal targeting of intact antibodies requires >24 h, therefore limiting the use of shortlived ␣ emitters. This study investigated the biodistribution of bismuth-labeled biotin in A431 tumor-bearing mice pretargeted with antibody B3-streptavidin (B3-SA) and examined the therapeutic efficacy of the ␣ emitter, 213Bi-labeled biotin. Experimental Design: Biotinidase-resistant 7,10-tetraazacyclododecane-N,N,N؆,Nٟ-tetraacetic acid (DOTA)-biotin was radiolabeled with 205,206 Bi or 213 Bi. Treatment of tumor-bearing mice began by administration of B3-SA (400 g) to target the tumor sites for 24 h. Then, an agent containing biotin and galactose groups was used to clear the conjugate from the circulation. Four h later, bismuth-radiolabeled DOTA-biotin was given, and biodistribution or therapy was evaluated. Dose escalation treatment from 3.7-74 MBq was performed, and the effects on tumors of different sizes were investigated. Tumor growth, complete blood cell counts, toxicity, and survival were monitored.Results: Radiolabeled biotin cleared rapidly. Rapid tumor uptake resulted in much higher tumor:nontumor targeting ratios than achieved with the directly labeled monoclonal antibody. Dose escalation revealed that 74 MBq caused acute death of mice, whereas 0.37-37 MBq doses inhibited tumor growth and prolonged survival significantly. Evidence of mild hematological toxicity was noted.At therapeutically effective doses renal toxicity was observed. Conclusions:213 Bi-DOTA-biotin, directed by the Pretarget method to tumor-targeted B3-SA, showed a therapeutic effect, although the therapeutic index was low. The source of the toxicity was most likely related to the renal toxicity.

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Section: Introductionmentioning

confidence: 99%

Pretargeted α Emitting Radioimmunotherapy Using 213Bi 1,4,7,10-Tetraazacyclododecane-N,N′,N″,N‴-Tetraacetic Acid-Biotin

Yao¹,

Zhang²,

Garmestani³

et al. 2004

Clinical Cancer Research

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“…In preclinical studies, 125 I-labeled mCOL-1 achieved good tumor radiolocalization using LS-174T colon carcinoma xenograft in athymic mice (30). In patients, 131 I-labeled mCOL-1 showed good tumor targeting of human gastrointestinal carcinomas in a phase I clinical trial (24). Not unexpectedly, mCOL-1 was found to induce HAMA response in patients (24,31).…”

mentioning

confidence: 98%

“…In patients, 131 I-labeled mCOL-1 showed good tumor targeting of human gastrointestinal carcinomas in a phase I clinical trial (24). Not unexpectedly, mCOL-1 was found to induce HAMA response in patients (24,31). Yu et al (24) reported that 61 and 83% of patients treated with the Ab developed elevated HAMA levels by days 20 and 40, respectively.…”

mentioning

confidence: 98%

Grafting of “Abbreviated” Complementarity-Determining Regions Containing Specificity-Determining Residues Essential for Ligand Contact to Engineer a Less Immunogenic Humanized Monoclonal Antibody

Pascalis

Itō

Tamura

et al. 2002

The Journal of Immunology

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Murine mAb COL-1 reacts with carcinoembryonic Ag (CEA), expressed on a wide range of human carcinomas. In preclinical studies in animals and clinical trials in patients, murine COL-1 showed excellent tumor localization. To circumvent the problem of immunogenicity of the murine Ab in patients, a humanized COL-1 (HuCOL-1) was generated by grafting the complementarity-determining regions (CDRs) of COL-1 onto the frameworks of the variable light and variable heavy regions of human mAbs. To minimize anti-V region responses, a variant of HuCOL-1 was generated by grafting onto the human frameworks only the “abbreviated” CDRs, the stretches of CDR residues that contain the specificity-determining residues that are essential for the surface complementarity of the Ab and its ligand. In competition RIAs, the recombinant variant completely inhibited the binding of radiolabeled murine and humanized COL-1 to CEA. The HuCOL-1 and its variant showed no difference in their binding ability to the CEA expressed on the surface of a CEA-transduced tumor cell line. Compared with HuCOL-1, the HuCOL-1 variant showed lower reactivity to patients’ sera carrying anti-V region Abs to COL-1. The final variant of the HuCOL-1, which retains its Ag-binding reactivity and shows significantly lower serum reactivity than that of the parental Ab, can serve as a prototype for the development of a potentially useful clinical reagent.

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“…Uptake of monoclonal antibodies in human tumour xenografts in nude mice is typically 5-40% DI g-' (Senekowitsch et al, 1989;Blumenthal et al, 1992;Siler et al, 1993), which contrasts with much lower uptakes of 0.001-0.01% DI g-of the same radiolabelled antibody in tumours of the same type in patients (Dykes et al, 1987;Begent et al, 1990;Yu et al, 1996). This uptake differential may also be due in part to the murine origin of most monoclonal antibodies developed for clinical use, for which the nude mouse is a syngeneic system.…”

mentioning

confidence: 99%

“…We have developed a large animal model of human cancer in immunosuppressed sheep in an attempt to circumvent the problems of the nude mouse model and avoid the subsequent disappointments of clinical trials of radioimmunotherapeutic agents that had been shown to effectively suppress human tumour xenografts in rodents (Yu et al, 1996). This study describes the development of a robust and practical large animal model of human tumours xenografted in cyclosporinimmunosuppressed sheep.…”

mentioning

confidence: 99%

Orthotopic xenografts of human melanoma and colonic and ovarian carcinoma in sheep to evaluate radioimmunotherapy

Turner

Rose²,

Glancy³

et al. 1998

Br J Cancer

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(CEA). The anti-CEA IgGl monoclonal antibody A5B7 was radiolabelled with iodine-131 and administered intravenously to sheep. Peak uptake at 5 days in orthotopic human tumour transplants in gut was 0.027% Dl g-' (percentage of injected dose per gram) and 0.034% Dl g-1 in hepatic metastases with tumour to blood ratios of 2-2.5. Non-specific tumour uptake in melanoma was 0.003% Dl g-1. Uptake of radiolabelled monoclonal antibody in human tumours in our large animal model is comparable with that observed in patients and may be more realistic than nude mice xenografts for prediction of clinical efficacy of radioimmunotherapy.

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Phase I trial of iodine 131-labeled COL-1 in patients with gastrointestinal malignancies: influence of serum carcinoembryonic antigen and tumor bulk on pharmacokinetics.

Abstract: 131I-COL-1 is well tolerated, except for hematologic toxicity. These data suggest that patients with highly elevated circulating CEA levels and/or increased tumor bulk may clear 131I-labeled COL-1 more rapidly from the circulation and experience less myelosuppression.

Cited by 28 publications

References 25 publications

Pretargeted α Emitting Radioimmunotherapy Using 213Bi 1,4,7,10-Tetraazacyclododecane-N,N′,N″,N‴-Tetraacetic Acid-Biotin

Pretargeted α Emitting Radioimmunotherapy Using 213Bi 1,4,7,10-Tetraazacyclododecane-N,N′,N″,N‴-Tetraacetic Acid-Biotin

Grafting of “Abbreviated” Complementarity-Determining Regions Containing Specificity-Determining Residues Essential for Ligand Contact to Engineer a Less Immunogenic Humanized Monoclonal Antibody

Orthotopic xenografts of human melanoma and colonic and ovarian carcinoma in sheep to evaluate radioimmunotherapy

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