Immunoscintigraphy in the follow-up of patients operated on for carcinoma of the sigmoid and rectum

Renda, Andrea; Salvatore, Marco; Sava, Mihai; Landi, Rosario; Lastoria, Secondo; Coppola, Leonardo; Schlom, Jeffrey; Colcher, David; Zannini, Giuseppa

doi:10.1007/bf02561688

Cited by 37 publications

(8 citation statements)

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“…The patterns of blood clearance of the aglycosylated and native chl4.18 mAbs in mice following i.v. In diagnostic tumor-targeting trials murine B72.3 has been administered to over 1000 patients with selective targeting to approximately 70%-80% of carcinomas [5,6,29]. The biodistribution of the ch14.18 and aglycosylated ch14.18 mAbs in mice was also similar.…”

Section: Introductionmentioning

confidence: 98%

Comparative biological properties of a recombinant chimeric anti-carcinoma mAb and a recombinant aglycosylated variant

Hand

Calvo

Milenic

et al. 1992

Cancer Immunol Immunother

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It has been demonstrated previously that the degree of glycosylation of a molecule may alter its pharmacokinetic properties and, in the case of an antibody, its metabolism and other biological properties. Transfectomas producing aglycosylated chimeric B72.3(gamma 1) pancarcinoma monoclonal antibody (mAb) were developed by introduction of the eukaryotic expression construct pECMgpB72.3 HuG1-agly, into SP2/0 murine myeloma cells producing the chimeric kappa chain of mAb B72.3. After cell cloning, one subclone with the highest binding to the TAG-72-positive human colon carcinoma was designated mAb aGcB72.3, and its biological and biochemical properties were compared with those of the chimeric B72.3(gamma 1), designated mAb cB72.3. Polyacrylamide gel electrophoresis showed that under non-reducing conditions, the molecular masses of the aGcB72.3 and cB72.3 mAbs were 162 kDa and 166 kDa respectively. The heavy chain of mAb aGcB72.3 had a slightly faster mobility than that of cB72.3, while the mobility of the light chains of the two chimeric mAbs was similar. No difference was observed in the isoelectric points of either chimeric mAb. Liquid competition radioimmunoassays demonstrated that the aGcB72.3 and cB72.3 mAbs have comparable binding properties to TAG-72. These studies demonstrate that aglycosylation of the chimeric IgG1 mAb B72.3 at the CH2 domain, as has been shown for other mAbs [Dorai H., Mueller B., Reisfeld R. A., Gillies S. D. (1991) Hybridoma 10:211; Morrison S. L., Oi V. T. (1989) Adv Immunol 44:65], eliminates antibody-dependent cell-mediated cytotoxicity activity, but does not substantially alter affinity or plasma clearance in mice. These studies also demonstrate for the first time (a) no difference in plasma clearance of an aglycosylated and a chimeric mAb in a primate after i.v. inoculation; (b) a difference (P less than or equal to 0.05) in mice in the more rapid peritoneal clearance of a chimeric mAb versus an aglycosylated chimeric mAb; (c) higher (0.05 less than or equal to P less than or equal to 0.1) tumor: liver ratios at 24, 72 and 168 h using 111In-labeled aglycosylated chimeric mAb versus chimeric mAb. Since the liver is the major site of metastatic spread for most carcinomas, slight differences in tumor to normal liver ratios may be important in diagnostic applications. These studies thus indicate that comparative analyses of a novel recombinant construct (i.e., aglycosylated) and its standard chimeric counterpart require documentation in more than one system and are necessary if one is ultimately to define optimal recombinant/chimeric constructs for diagnosis and therapy in humans.

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Section: Introductionmentioning

confidence: 98%

Comparative biological properties of a recombinant chimeric anti-carcinoma mAb and a recombinant aglycosylated variant

Hand

Calvo

Milenic

et al. 1992

Cancer Immunol Immunother

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“…Our experience dealt with 52 cases of which 48 were colorectal carcinomas, representing 15% of the patients who underwent surgery between 1989 and 1996 for this disease [5][6][7]. Patients underwent radioimmunoguided --10 rectum B -" --11 caecum D + " liver yes metastasis 12 sigmoid C + " --13 left D + " peritoneal no metastasis 14 rectum B + " --15 rectum Recurrence + " --16 right colon B -" --17 rectum C + " lymph node no involvement 18 sigmoid D + " pelvic no involvement 19 caecum C + " --20 rectum D + " uterine no involvement 21 rectum C + " --22 rectum C + " --23 rectum B + False positive --*RIGS, radioimmunoguided surgery; intraop., intraoperative.…”

Section: Introductionmentioning

confidence: 99%

Radioimmunoguided surgery in colorectal cancer: A 6-year experience with four different technical solutions

Renda

Iovino

Capasso

et al. 1998

Semin. Surg. Oncol.

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“…Twenty-six patients with primary colorectal cancer and 72 patients with recurrent colorectal cancer were examined. Using the gamma detecting probe, 78% of the patients had localization of the antibody in their tumor; this included 75% of primary tumor sites and 63% of all recurrent tumor sites; 9.2% of all tumor sites identified represented occult sites detected only with the gamma detecting probe. The overall sensitivity was 77% and a predictive value of a positive detection was 78%.…”

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confidence: 99%

Radioimmunoguided Surgery Using Iodine 125 B72.3 in Patients With Colorectal Cancer

Cohen

Martin²,

Lavery³

et al. 1991

Arch Surg

103

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Preliminary data using B72.3 murine monoclonal antibody labeled with iodine 125 suggested that both clinically apparent as well as occult sites of colorectal cancer could be identified intraoperatively using a hand-held gamma detecting probe. We report the preliminary data of a multicenter trial of this approach in patients with primary or recurrent colorectal cancer. One hundred four patients with primary, suspected, or known recurrent colorectal cancer received an intravenous infusion of 1 mg of B72.3 monoclonal antibody radiolabeled with 7.4 x 10 Bq of iodine 125. Twenty-six patients with primary colorectal cancer and 72 patients with recurrent colorectal cancer were examined. Using the gamma detecting probe, 78% of the patients had localization of the antibody in their tumor; this included 75% of primary tumor sites and 63% of all recurrent tumor sites; 9.2% of all tumor sites identified represented occult sites detected only with the gamma detecting probe. The overall sensitivity was 77% and a predictive value of a positive detection was 78%. A total of 30 occult sites in 26 patients were identified. In patients with recurrent cancer, the antibody study provided unique data that precluded resection in 10 patients, and in another eight patients it extended the potentially curative procedure.

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Immunoscintigraphy in the follow-up of patients operated on for carcinoma of the sigmoid and rectum

Cited by 37 publications

References 1 publication

Comparative biological properties of a recombinant chimeric anti-carcinoma mAb and a recombinant aglycosylated variant

Comparative biological properties of a recombinant chimeric anti-carcinoma mAb and a recombinant aglycosylated variant

Radioimmunoguided surgery in colorectal cancer: A 6-year experience with four different technical solutions

Radioimmunoguided Surgery Using Iodine 125 B72.3 in Patients With Colorectal Cancer

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