Localisation and toxicity study of a vindesine-anti-CEA conjugate in patients with advanced cancer

Ford, C. H. J.; Newman, C.E.; Johnson, James R.; Woodhouse, Clive S.; Reeder, T A; Rowland, G. F.; Simmonds, R.G.

doi:10.1038/bjc.1983.4

Cited by 96 publications

(48 citation statements)

References 17 publications

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“…Some of the earlier iterations of ADCs tested in the clinic included the incorporation of antimitotics and antimetabolites approved for use in chemotherapy as unconjugated cytotoxins (Ford et al, 1983;Oldham et al, 1988;Elias et al, 1990;Petersen et al, 1991;Krauer et al, 1992;Takahashi et al, 1993). These early clinical ADCs suffered from a panoply of issues, not the least of which was a drug likely too impotent for targeted delivery.…”

Section: A Doxorubicinmentioning

confidence: 99%

Antibody Drug Conjugates for Cancer Therapy

2015

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Section: A Doxorubicinmentioning

confidence: 99%

Antibody Drug Conjugates for Cancer Therapy

2015

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“…The use of anti-CEA monoclonal antibodies tagged with a chemotherapeutic agent after successful localization with radiolabeled antibody has been shown to be feasible. 22 Monoclonal antibodies tagged with a beta-emitter have also been used for more specific radiation the rap^.^^.^^ Since smaller tumors have a larger tumor uptake per gram compared with the liver, monoclonal antibodies tagged with a beta-emitter of chemotherapeutic agent would be more useful in small metastases, or possibly adjuvant to surgical resection of locally advanced disease.…”

Section: Cancer February I 1986mentioning

confidence: 99%

The effect of tumor CEA content and tumor size on tissue uptake of indium 111-labeled anti-CEA monoclonal antibody

Philben

Jakowatz

Beatty

et al. 1986

Cancer

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This study was undertaken to determine the effect of tumor size and tumor carcinoembryonic antigen (CEA) content on the uptake of indium 111 (111In)‐labeled anti‐CEA monoclonal antibody in nude mice bearing xenografts. The tumor cell lines were WiDr, SW403, and LS174T, human colon cancer derivatives. The murine breast carcinoma cell line EMT‐6 was used as a control. Tumor CEA levels (ng/g) of tumor standard error of the mean [SEM], measured by enzyme immunoassay (EIA) were: EMT‐6, 0; WiDr, 105 ± 5.7; LS174T, 2052 ± 198; SW403, 17,575 ± 1,785. The 111In‐labeled monoclonal antibody was injected intravenously into mice bearing a single tumor. At 48 hours postinjection, scintiscan was performed, and the mice were killed so that biodistribution studies could be performed. The uptake of the monoclonal antibody was expressed as percent injected counts per minute per gram of tissue ± SEM. The non‐CEA‐producing tumor, EMT‐6, showed the lowest tumor uptake (1.4 ± 0.3). WiDr, an intermediate CEA‐producing tumor, showed some tumor uptake (16.4 ± 1.5). The high CEA‐producing tumors, SW403 and LS174T, had high tumor uptake (29.5 ± 5.0 and 51.1 ± 6.1, respectively). Biodistribution and scintiscan quality were closely related. Although LS174T had the best tumor uptake, SW403 had the highest CEA tumor content, indicating tumor CEA content cannot entirely predict scintiscan and biodistribution results. Tumor‐to‐blood (T/B), tumor‐to‐liver (T/L), and liver‐to‐blood (L/B) ratios were calculated for each animal and compared with tumor size. It was found that T/L had a negative correlation with tumor size (r = −0.72) and L/B had a positive correlation with tumor size (r = 0.94). These ratios may be useful clinically to follow response to therapy.

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“…Ford et al have given patients sheep anti-CEA antibody conjugated with vinblastine [10], though no clinical benefit was reported. Only 6 of the treated patients received more than 10 mg of antibody with a maximum dosage of 41 mg of antibody.…”

Section: Discussionmentioning

confidence: 99%

Non-human primate (baboon) anti-carcinoembryonic antigen antibody infusion in patients with metastatic adenocarcinoma

Huberman

Lokich

Hill

et al. 1986

Cancer Immunol Immunother

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A total of 14 patients with advanced visceral carcinoma which produced carcinoembryonic antigen (CEA) were treated in a Phase I study with IV infusion of affinity purified baboon anti-CEA antibody (dosage range from 0.1 to 2 mg/kg body weight). In all 14 patients, the antibody infusion caused a decrease (26% to 97%) in the plasma level of CEA. The degree of decrease depended upon the patients initial CEA level and the amount of antibody given. In 12 of the 14 patients "free" circulating antibody was observed. The plasma half-life of the antibody ranged from 0.7 to 21 h and the duration of detectable free antibody ranged from 3 to 216 h postinfusion. No toxicity was observed for the dosage range of antibody tested. In 9 of the 14 patients a low titer anti-baboon antibody response occurred between 14 and 28 days postinfusion. No clinical regression of carcinoma was documented. In 7 of the 14 patients disease remained stable during the 28-day study period. By the end of the 28-day study period plasma CEA levels had returned to at least the preinfusion level in 11 of the 14 patients.

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Localisation and toxicity study of a vindesine-anti-CEA conjugate in patients with advanced cancer

Abstract: Summary Safety of administration of a vindesine (VDS)-anti-CEA conjugate and its ability to localise after radiolabelling were investigated in patients with advanced metastatic carcinoma (4 colorectal and 4 ovarian).

Cited by 96 publications

References 17 publications

Antibody Drug Conjugates for Cancer Therapy

Antibody Drug Conjugates for Cancer Therapy

The effect of tumor CEA content and tumor size on tissue uptake of indium 111-labeled anti-CEA monoclonal antibody

Non-human primate (baboon) anti-carcinoembryonic antigen antibody infusion in patients with metastatic adenocarcinoma

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