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E Berrie

Publications and source records attributed to E Berrie.

7 recordsLinked to original sources
PubMed2004

Design and manufacture of monoclonal antibodies for radioimmunotherapy.

antibodies is fundamental to their use for radioimmunotherapy. Besides the right selection of antibody specificity and affinity, recombinant antibodies can be designed to simplify manufacture and minimise unwanted side effects. Although many innovative new technologies have been developed in recent years, antibodies are still most commonly produced from mammalian cells and purified by column chromatography. Purification methods have to be designed and validated to remove potential contaminants, especially retroviruses, which in principle might be present in mammalian cell lines. Adherence to relevant ''Good Manufacturing Practices'' is mandatory in the production of any medicinal product and there are numerous guidelines regarding the manufacture of antibodies. This article outlines some methods used for fermentation, purification and quality control of antibodies intended for radiolabelling.

Animals↗
PubMed2001

Manufacture and quality control of CAMPATH-1 antibodies for clinical trials.

BACKGROUND: CAMPATH-1 Abs have been used for T-cell depletion in stem-cell transplantation since the early 1980s. During that time there has been substantial progress in manufacturing techniques and quality control procedures. This article summarizes the methods used to produce the Abs for clinical use and describes results of quality control tests on representative batches. METHODS: Rat hybridoma and recombinant CHO cells were cultured in hollow-fiber fermentors. Antibodies were purified from the culture supernatant by fractionation with ammonium sulphate, or by column chromatography. Additional steps were added to assure the removal of DNA and viruses. A range of analytical methods was used to characterize the antibodies. Samples were stored frozen at -70 degrees C and re-analyzed many years later to assess the long-term stability. RESULTS: Hollow-fiber fermentors provided a simple and reliable means for antibody production, with yields between 3-10 mg/h and a convenient concentration for further processing (0.6-2.0 mg/mL). All of the CAMPATH-1 Abs (rat IgM, rat IgG2b and human IgG1) could be purified by affinity chromatography on Protein A, but the low pH required for elution caused unacceptable aggregation of the IgM. CAMPATH-1H contained approx. 20% dimeric IgG, which could be removed by size exclusion chromatography. Antibodies were stable for at least 6 years at -70 degrees C, but there was unacceptable aggregation of CAMPATH-1M in one batch stored for 9 years. DISCUSSION: Pilot-scale production of MAbs for clinical studies is feasible in a small academic center, but regulatory requirements now demand that great attention is paid to all aspects of manufacturing and quality assurance. Although the underlying principles of cell culture and protein chemistry remain the same, the level of documentation, validation and quality control has increased greatly over the last 20 years.

Alemtuzumab↗
PubMed1986

Three-year prospective study of HTLV-III/LAV infection in homosexual men.

170 symptom-free homosexual men were recruited in London in 1982-83 and 133 were evaluable in 1983-85. Of the 33 who were seropositive to HTLV-III/LAV at entry, 4 (12%) progressed to AIDS, 16 (48%) progressed to persistent generalised lymphadenopathy (PGL), and 13 (40%) remained symptom-free. A further 15 men seroconverted during the study (7% per annum), of whom 8 progressed to PGL. Serial estimations of T lymphocyte subsets showed progressive reduction in T4 numbers in the seropositive groups, but these indices also varied widely in the seronegative group. Counts of T4 and T8 cells or T4/T8 ratio at entry were not of prognostic value. Seronegative subjects were as likely as seropositives to have abnormal immunological tests. Serial measurement of T lymphocyte subsets seems to be of little prognostic or clinical value in the monitoring of populations infected with the HTLV-III/LAV virus. The strongest association with prognosis was an episode of sexually transmitted disease in the six months before entry to the study. This supports the hypothesis that intercurrent infection may be an important co-factor in the acquisition of HTLV-III/LAV infection, and in subsequent disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Factors affecting seropositivity to human T cell lymphotropic virus type III (HTLV-III) or lymphadenopathy associated virus (LAV) and progression of disease in sexual partners of patients with AIDS.

Fifty four sexual partners of homosexual men with the acquired immune deficiency syndrome (AIDS) were studied, of whom 32 were seropositive and 22 seronegative for human T cell lymphotropic virus type III or lymphadenopathy virus (HTLV-III/LAV) antibody, which showed that repeated exposure by anal intercourse does not necessarily lead to seroconversion. Seropositivity to HTLV-III/LAV was not associated with the absolute number of sexual partners, receptive anal intercourse, or the use of recreational drugs, but was associated with a history of other sexually transmitted diseases (STDs), particularly in the year preceding the patient's initial examination. Acquisition of an STD after the date of last sexual contact with a person with AIDS was strongly associated (p less than 0.001) with the development of persistent generalised lymphadenopathy (PGL). Concurrent or recent STDs would seem to be an important cofactor in developing antibody to HTLV-III/LAV and in the progression of infection from a person being asymptomatic to having PGL.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Transmission of a malignant catarrhal fever-like syndrome to sheep: preliminary experiments.

The transmission of a malignant catarrhal fever-like syndrome to sheep is reported. Fetal sheep between 40 and 66 days gestation were inoculated intravenously with viable cells either from a red deer with clinical malignant catarrhal fever or from rabbits with the disease. Of the 21 fetuses in the experiment only five were born live and of these four developed clinical signs similar to malignant catarrhal fever in other species and died or were killed 10, 16, 47 and 175 days after birth. The fifth lamb remained unaffected. Histology of the four affected lambs revealed a generalised lymphoproliferation, with T-dependent areas of lymphoid tissues being affected, and an overall paucity of immunoglobulin containing cells. In addition arteritis and interstitial infiltration of many organs by lymphoid cells was present. The infectious agent was not reisolated in rabbits from lambs or passed to red deer housed in the same pen and it is thus considered possible that gene expression of the putative virus was incomplete.

Animals↗
PubMed1984

Malignant catarrhal fever.

Malignant catarrhal fever is briefly reviewed and recent findings are described. Initially the disease was observed as a disease of cattle in Europe where, although no cause could be identified, circumstantial evidence implicated sheep as a source of infection and it was thus designated 'sheep-associated' malignant catarrhal fever. Subsequently the disease was observed in Africa where it became evident that a herpesvirus which normally infects wildebeest was the cause. It is now apparent that deer are highly susceptible to both forms of the disease, the sheep-associated form being a serious problem in farmed deer. The wide spectrum of clinical and pathological changes that occur in affected deer are described. A major constraint to studies of sheep-associated malignant catarrhal fever has been the absence of an experimental laboratory system. However, from affected deer it has been possible to transmit the disease to rabbits and thus has allowed detailed pathogenesis studies to be made which are summarised in this paper. It is suggested that the agent of sheep-associated malignant catarrhal fever is a virus and that when a particular subpopulation of T-lymphocytes is infected a profound immunological perturbation results; the lesions of malignant catarrhal fever being explained by a benign T-lymphocyte hyperplasia accompanied by a deregulation of cytotoxic natural killer lymphocytes that gives rise to tissue necrosis.

Animals↗