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- Riklund, Katrine, et al.
(författare)
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A putative mechanism for the non-specific uptake of intact radiolabelled monoclonal antibodies in the testes and prostate.
- 1996
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 35:3, s. 303-307
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Tidskriftsartikel (refereegranskat)abstract
- Non-specific testicular accumulation of radiolabelled intact anti-CEA monoclonal antibody (MAb), (A431/26, Behringwerke AG) was observed in 11 out of 12 patients with the testes and prostate included in the examination field at radioimmunoscintigraphy (RIS). Previous studies have shown that placental alkaline phosphatase (PLAP) serves as an Fc-receptor, mediating IgG transport through the placenta. A closely related protein, the germ cell alkaline phosphatase (GCAP), is expressed in the testes. The testicular uptake of IgG is observed only when intact but not fragmented MAbs are used, indicating involvement of Fc-receptors. MDCK cells (dog kidney cell line) transfected with the plasmid pSVT7 containing the GCAP gene were shown to acquire the capacity to both express membrane bound GCAP and to bind IgG on the cell surface. This might indicate that GCAP is responsible for the non-specific accumulation of intact MAb in the testes and prostate often observed when intact murine MAbs are used for radioimmunolocalization (RIL).
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| 4. |
- Riklund, Katrine, et al.
(författare)
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Experimental radioimmunotherapy of HeLa tumours in nude mice with 131I-labeled monoclonal antibodies.
- 1990
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 10:2A, s. 379-84
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Tidskriftsartikel (refereegranskat)abstract
- The radioimmunotherapeutic potential of 131I-labeled monoclonal antibodies was investigated in 36 nude mice (BALB/c nu/nu) inoculated s.c. with the HeLa Hep 2 human adenocarcinoma cell line. The membrane bound tumour associated antigen placental alkaline phosphatase and several intracellular cytokeratins served as targets for the antibodies. The specific radioactivity in each organ was determined after i.p. injection of the 131I-labeled antibodies (0.2-0.3 mg, approximately 15 MBq/animal), and high localization to the tumours was seen. Significant growth inhibition was observed after injection of the radiolabeled monoclonal antibody H7 against the placental alkaline phosphatase, which reduced the tumour growth to only 12% during a 3 week period compared to a growth of more than 100% for the controls. Animal weight losses were seen. Synthesis of endogenous antibodies to the target antigens was found to be significant. Morphometric evaluation of the relations between stroma, tumour cells and necrotic areas in the tumours after radioimmunotherapy demonstrated a significant increase of the mean relative connective tissue volume and a significant decreased mean of relative volume of tumour cells in the group treated with iodinated antiplacental alkaline phosphatase antibody. This therapeutic principle is encouraging and may offer new possibilities for future treatment of some malignant diseases.
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| 5. |
- Riklund, Katrine, et al.
(författare)
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Inhibition of growth of HeLa cell tumours in nude mice by 125I-labeled anticytokeratin and antiPLAP monoclonal antibodies.
- 1991
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 11:2, s. 555-560
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Tidskriftsartikel (refereegranskat)abstract
- The radiommunotherapeutic potential of 125I-labeled monoclonal antibodies was investigated in 48 nude mice (BALB/c, nu/nu) inoculated s.c. with the HeLa Hep 2 human adenocarcinoma cell line. This isotope, 125I, which is not commonly used for therapeutic purposes caused significant decrease in tumour growth from day 10 to day 42, when coupled to monoclonal antibodies directed against placental alkaline phosphatase (H7) or cytokeratins (TS1). The average growth rate was approximately 50-60% of that observed in the untreated control group after 42 days. The specific radioactivity in each organ 42 days after injection of radiolabeled monoclonal antibodies, indicated that these target antigens retain significant amounts of radiolabeled antibody in the tumours for at least 6 weeks after injection. No weight loss was seen in the animals during this experiment. By use of autoradiographic techniques, the labeled monoclonal antibodies were visualized deep in tumours in characteristic patterns representative of viable tumour cells (H7) and necrotic areas (TS1). The therapeutic approach using 125I labeled antibodies is encouraging and may offer new dimensions in radioimmunotherapy.
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| 6. |
- Riklund, Katrine, et al.
(författare)
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Radioimmunoscintigraphy of gynecologic tumors with 131I-labeled anti-PLAP monoclonal antibodies.
- 1991
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Ingår i: Acta Radiologica. - 0284-1851 .- 1600-0455. ; 32:5, s. 375-380
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Tidskriftsartikel (refereegranskat)abstract
- Radioimmunoscintigraphy (RIS) was performed in 20 patients with gynecologic tumors, 14 ovarian, 5 cervical, and one endometrial carcinoma. One murine monoclonal antibody (mab) against placental alkaline phosphatase (H7) was used after radiolabeling with 131I. The labeling procedure yielded antibodies with specific activity varying between 60 and 73 MBq/mg mab. Each patient received 57 to 100 MBq of the preparation. RIS was performed 7 to 35 days later. Patients with ovarian adenocarcinoma had an accumulation of activity on RIS at tumor sites (79%, 11/14) verified by ultrasonography, CT, and clinical examination. A low or absent accumulation of activity was seen in patients with cervical tumors. The patient with an endometrial adenocarcinoma was seen to have an activity accumulation at RIS corresponding to tumor sites determined by ultrasound and/or CT. It is concluded that RIS using monoclonal antibodies against placental alkaline phosphatase can provide information which will supplement that gained from other investigations of patients with ovarian adenocarcinomas.
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- Stigbrand, Torgny, et al.
(författare)
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Alternative technologies to generate monoclonal antibodies.
- 1993
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 32:7-8, s. 841-844
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Tidskriftsartikel (refereegranskat)abstract
- Several new technologies to generate and modify established hybridomas that produce monoclonal antibodies have recently been presented and further development should make them more suitable for diagnostic and therapeutic techniques. Different proteolytic procedures have been used for the fragmentation of intact antibodies to Fab2' and Fab fragments and recombinant DNA techniques have made it possible to obtain chimeric, humanized, Fv fragments and single-chain Fvs. A review of the new approaches is presented and the future implications are discussed.
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| 10. |
- Stigbrand, Torgny, et al.
(författare)
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Tumour radioimmunolocalization in nude mice by use of antiplacental alkaline phosphatase monoclonal antibodies.
- 1989
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Ingår i: Tumor Biology. - 1010-4283 .- 1423-0380. ; 10:5, s. 243-251
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Tidskriftsartikel (refereegranskat)abstract
- Three monoclonal antibodies and their Fab and Fab'2 fragments with specificity against human placental alkaline phosphatase (PLAP) were evaluated for tumour immunolocalization of human PLAP-producing Hela Hep 2 tumours in nude mice. The antibodies and their fragments were labelled with 125I and injected intraperitoneally in mice with developing Hep 2 tumours. The animals were followed individually for 14 days with repetitive computerized gamma-camera recordings, which enable quantitation of several crucial parameters, i.e. the time-dependent antibody uptake in the tumours, decrease in background activity and tumour/background ratio. Excellent radioimmunolocalization was obtained with both the intact PLAP-specific immunoglobulins and their fragments but not with the nonspecific antibodies. No background subtraction had to be used. As much as 15% of the initially injected dose could be visualized in the tumours and for the uncleaved mab up to 80% of the radioactivity in the animals was retained in the tumours after 14 days, a considerably longer observation time than usually reported in such tumour xenograft models. The Fab and Fab'2 fragments were found to be excreted fast with less than 5% of the injected dose remaining in the animals after 48 h, but still with positive specific localization to the tumours after an initial high uptake in the kidneys. The results are encouraging and indicate significant potentials of the PLAP-antiPLAP mab system for immunolocalization studies in patients.
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