Drug localisation and growth inhibition studies of vindesine-monoclonal anti-CEA conjugates in a human tumour xenograft

Rowland, G. F.; Simmonds, R.G.; Gore, Vivek; Marsden, C. H.; Smith, William K.

doi:10.1007/bf00199359

Cited by 42 publications

(22 citation statements)

References 12 publications

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“…Xenograft growth was initiated by S.C. inoculation of 0.2 ml of a suspension of MAWI, a human colorectal carcinoma (Rowland et al, 1986). …”

Section: Mice and Xenograftsmentioning

confidence: 99%

Tumour therapy with vinca alkaloids targeted by a hybrid-hybrid monoclonal antibody recognising both CEA and vinca alkaloids

Corvalan¹,

Smith²,

Gore³

1988

Int. J. Cancer

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The functional properties of a hybrid-hybrid monoclonal antibody (MAb) recognising both CEA and Vinca alkaloids have been explored in vivo in nude mice xenografted with MAWI, a human colorectal turnour. The hybrid-hybrid MAb localises specifically onto CEA-expressing tumour tissue and, furthermore, is able to target Vinca alkaloids to turnour. Under the influence of the hybrid-hybrid MAb a profound change in the bio-distribution patterns of the Vinca alkaloids is observed. Therapeutic data produced in this in vivo model indicates that treatment with Vinca alkaloids in conjunction with hybrid-hybrid MAb is significantly more effective in suppressing tumour growth of established tumour xenografts than the Vincas when given as free drug.The covalent coupling of drugs or toxins to tumour-specific MAbs and their potential use as therapeutic agents has been actively explored in the recent past as a way to overcome the inherent lack of specificity associated with conventional chemotherapy. Conjugates of vindesine with MAbs recognising osteosarcoma, melanoma or carcinoembryonic antigens have shown therapeutic potential with reduced drug toxicity (Rowland et al., 1985), although these (19874 using a hybrid-hybrid MAb with specificity to both the tumour-associated antigen and the cytotoxic drug. In this model the drug is delivered to the tumour through the antigen-combining site of the bispecific antibody. We report here that drug delivered in such a way is far more efficacious than an equivalent amount of free drug. MATERIAL AND METHODS Mice and xenograftsOutbred nu/nu athymic mice were bred and maintained in isolators (Isotec, Bicester, UK). Xenograft growth was initiated by S.C. inoculation of 0.2 ml of a suspension of MAWI, a human colorectal carcinoma (Rowland et al., 1986). Hybrid-hybrid monoclonal antibodyThe construction, affinity purification and the in vitro and in vivo properties of the hybrid-hybrid 28.19.8 MAb have been described (Corvalan et al., 1987a, b and c). For in vivo studies affinity purified 28.19.8 MAb was stored at 1 mg/ml in phosphate buffered saline (PBS), filtered sterile (0.2 pm) and maintained at 4°C until used. Further dilutions were made in PBS shortly before use. 3H-Vinblastine in in vivo localisation studiesGroups of 3 mice with 3-4 weeks established MAWI xenografts were injected i.p. with 1 mg of affinity purified hybrid-hybrid 28.19.8 MAb or PBS for the control group either at 7 or 3 days before, or on the same day as a mixture of vinblastine sulphate (VLB) and 3H-VLB (Amersham International, Little Chalfont, UK) as tracer. At days 1 and 7 after the injection, mice were killed and dissected. Weighed samples of tumour, visceral organs and plasma were then transferred to scintillation vials, processed (Rowland et al., 1986), and counted using a beta counter (1217 Rackbeta, LKB-Wallac, Bromma, Sweden). The results were expressed as nanograms of VLB localised per gram of tissue. In vivo turnour inhibition studiesThe in vivo effects of Vinca alkaloids targeted to tumour by hybrid-hybrid 28.19...

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“…Xenograft growth was initiated by S.C. inoculation of 0.2 ml of a suspension of MAWI, a human colorectal carcinoma (Rowland et al, 1986). …”

Section: Mice and Xenograftsmentioning

confidence: 99%

Tumour therapy with vinca alkaloids targeted by a hybrid-hybrid monoclonal antibody recognising both CEA and vinca alkaloids

Corvalan¹,

Smith²,

Gore³

1988

Int. J. Cancer

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“…Such mAbs have been used as carriers of most of the clinically used anticancer agents (5)(6)(7)(8) and also for highly potent toxin molecules such as the A-chain toxins (3). The purpose of much of this work has been to increase the therapeutic effect of the cytotoxic agent by enhancing its localization in the target tissue and, at the same time, to spare the nontarget tissues from its toxic effects.…”

mentioning

confidence: 99%

Anti-tumor effects of antibody-alkaline phosphatase conjugates in combination with etoposide phosphate.

Senter

Saulnier

Schreiber

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

206

106

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“…Vindesine (a vinca alkaloid) has been conjugated with different anti-tumour antibodies, such as anti-CEA, melanoma, osteosarcoma and others (79)(80)(81)(82). Studies with vindesine-anti-CEA conjugates (82) indicate that they increase the therapeutic index of vindesine by decreasing the toxicity and increasing the specificity to tumour. These findings were substantiated by Casson et al (83).…”

Section: Vinca Alkaloidsmentioning

confidence: 99%

Monoclonal antibodies in drug targeting

Panchagnula

Dey

1997

Journal of Clinical Pharmacy and Therapeutics

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SUMMARYThe objective of drug targeting is to deliver drugs to a specific site of action through a carrier system. In cancer chemotherapy, cytotoxic drugs kill cancerous cells but also damage normal cells. Monoclonal antibodies generated against specific antigens, when conjugated to cytotoxic drugs, can selectively deliver drugs to cancer cells while minimizing damage to normal cells. Of all the carrier systems available, monoclonal antibodies are gaining importance because of their high specificity. The purpose of this review is to provide a comprehensive account of the use of monoclonal antibodies in drug targeting, highlighting their scope and limitations.

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Drug localisation and growth inhibition studies of vindesine-monoclonal anti-CEA conjugates in a human tumour xenograft

Cited by 42 publications

References 12 publications

Tumour therapy with vinca alkaloids targeted by a hybrid-hybrid monoclonal antibody recognising both CEA and vinca alkaloids

Tumour therapy with vinca alkaloids targeted by a hybrid-hybrid monoclonal antibody recognising both CEA and vinca alkaloids

Anti-tumor effects of antibody-alkaline phosphatase conjugates in combination with etoposide phosphate.

Monoclonal antibodies in drug targeting

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