Antibody as carrier of chlorambucil

Ghose, T.; Path, M. R. C.; Nigam, Shubhanchi

doi:10.1002/1097-0142(197205)29:5<1398::aid-cncr2820290542>3.0.co;2-d

Cited by 101 publications

(11 citation statements)

References 4 publications

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“…1 However, it took 45 years for such a species to be constructed in the form of an ADC. 2 In the 1970's, ADCs were first tested on animals 3,4 and less than a decade later the first tests on humans showed promising results. 5 The first ADCs based on chimeric and humanised monoclonal antibodies (mAbs) were reported in the 1990s, 6 and throughout this decade, ever increasing payload potency and improved target selection were achieved.…”

Section: Introductionmentioning

confidence: 99%

Recent advances in the construction of antibody–drug conjugates

2016

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Antibody-drug conjugates (ADCs) comprise antibodies covalently attached to highly potent drugs using a variety of conjugation technologies. As therapeutics, they combine the exquisite specificity of antibodies, enabling discrimination between healthy and diseased tissue, with the cell-killing ability of cytotoxic drugs. This powerful and exciting class of targeted therapy has shown considerable promise in the treatment of various cancers with two US Food and Drug Administration approved ADCs currently on the market (Adcetris and Kadcyla) and approximately 40 currently undergoing clinical evaluation. However, most of these ADCs exist as heterogeneous mixtures, which can result in a narrow therapeutic window and have major pharmacokinetic implications. In order for ADCs to deliver their full potential, sophisticated site-specific conjugation technologies to connect the drug to the antibody are vital. This Perspective discusses the strategies currently used for the site-specific construction of ADCs and appraises their merits and disadvantages.

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Section: Introductionmentioning

confidence: 99%

Recent advances in the construction of antibody–drug conjugates

2016

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“…The findings of direct immunofluorescence staining were further confirmed by the sandwich method, treating sections first with unconjugated reagents and then, as appropriate, with fluoresceinated goat antirabbit globulin or rabbit antigoat globulins with proper controls (Ghose, Nairn, and Cerini, I968; Ghose and Nigam, 1972;McGiven, Ghose, and Nairn, I967). The "sandwich" immunofluorescence method was used also for the detection of antinuclear, antithyroid, and antiuveal tract antibodies, using undiluted and diluted sera, i.e.…”

Section: Methodsmentioning

confidence: 86%

Immunoglobulins in aqueous humour and iris from patients with endogenous uveitis and patients with cataract.

Ghose¹,

Quigley²,

Landrigan³

et al. 1973

British Journal of Ophthalmology

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The scarcity of aqucous humour and uveal tissues from living patients has hampered studies on the immunological aspects of human eye diseases. There are many autopsy studies investigating the niature and amount of proteins in human aqueous, but it is known that the composition of aqueous humour changes very rapidly after death so that the validity of the results of these autopsy studies on the composition of aqueous humour is in doubt (Hemmingsen and Other, I967; Dieckhues, I967; Allansmith, Whitney, McClellan, and Newman, I973). Application of radial immunodiffusion (Mlancini, Carbonara, and Heremans, I965) has enabled us to estimate quantitatively IgG, IgMl, and IgA in the aqueous humour obtained before surgery from patients suffering from: (i) Active chronic endogenous uveitis, (ii) Narrow-angle glaucoma with no active inflammation, (iii) Senile cataracts.Small pieces of iris were also available from these patients for immunohistochemical study. Material and methodsSamples of aqueous humour collected just before surgery, taking care not to contaminate the aqueous with blood, were centrifuged in small glass test-tubes (6 mm. diameter with conical bottom) at i,ooo G. max. for I o min. to get rid of cells and tissue debris (if any). The clear supernatant was subjected to radial immunodiffusion in plates (Hyland Laboratories, California). Using a numbei of reference standards supplied by the Hyland Laboratories and the World Health Organization (W.H.O. Standard 67 87), the lowest protein concentrations which could be reliably measured by this method were: IgG, 5 mg./I00 ml.; 1gM, 4 mg. I00 ml.; IgA, 4 mg./ I00 ml.To assess the reproducibility of this method of immunoglobulin determination, ten repeated measurements of each of the three immunoglobulin classes were performed on a diluted pooled specimen of normal human serum. The coefficient of variation (standard deviations/mean concentration x ioo) of the IgG, IgM, and IgA determinations respectively were ±6, ±4, and ±7 pel cciet. Whenever the volume of aqueous humour was insufficient, the aqueous was subjected to immunoelectrophoresis against an antibody to whole human serum for qualitative detection of immunoglobulin fractions.Freshly excised pieces of iris (about 2 CU. mm.) were snapfiozen in a slurry of liquid nitrogen and isopentane (-i6oC.) and stored at 70°C. Air-dried unfixed 2 to 3 L cryostat sections of iris as well as parallel sections fixed in 5 per cent. glacial acetic acid in ethanol at -20°C. for I5 min.(Hijmans, Schuit, and Klein, I969) were washed three times in phosphate buffered saline (PBS,

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“…During the past 20 years, many groups have used this new approach for coupling agents such as chlorambucil (3,4), methotrexate (5,6). mitomycin C (7,8), toxins (9,10) and anthracyclinediones (11,12).…”

Section: T He Use Of Cytotoxic Drugs For the Treatment Ofmentioning

confidence: 99%

Conjugation of Daunorubicin to Monoclonal Antihuman Sarcoma Antibody by a Novel Method

Page¹,

Thibeault²,

Tremblay³

et al. 1992

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Conjugation of daunorubicin to monoclonal antihuman sarcoma antibody by a novel method. Can J Infect Dis 1992;3(Suppl B): 101B-105B. Most of the reported methods for coupling anthracycline drugs to antibody result in either a loss of pharmacological activity or yield antibodies which have lost much of their immunological specificity. The use of glutaraldehyde for coupling saves both the pharmacological and immunological activities but it causes some polymerization of the antibody or of the macromolecular carrier which is undesirable for in vivo use. A new coupling procedure is reported which uses an activated derivative of daunorubicin added to monoclonal antihuman sarcoma antibody. This coupling procedure has not resulted in significant polymerization of the antibody or Joss of ph armacological activity determined by testing normal and tumour cell L ines in vitro.

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Antibody as carrier of chlorambucil

Cited by 101 publications

References 4 publications

Recent advances in the construction of antibody–drug conjugates

Recent advances in the construction of antibody–drug conjugates

Immunoglobulins in aqueous humour and iris from patients with endogenous uveitis and patients with cataract.

Conjugation of Daunorubicin to Monoclonal Antihuman Sarcoma Antibody by a Novel Method

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