Strategy for the production of human monoclonal antibodies using in vitro activated B cells

Borrebaeck, Carl

doi:10.1016/0022-1759(89)90219-6

Cited by 61 publications

(27 citation statements)

References 26 publications

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“…For the bioreactivity studies physiological PBLs from blood donors were used in order to mimic more realistically an in vivo situation. 10 Although the presence of the co-polymers in PBL cultures did not induce any noticeable activation as expected, quantitative differences were observed in cell proliferation when the cells were stimulated polyclonally or via antigen presentation when certain co-polymers were present. The same differences were observed in immunoglobulin secretion.…”

Section: Assessment Of the Co-polymer Reactivitymentioning

confidence: 80%

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Light scattering and in vitro biocompatibility studies of poly (vinyl pyrrolidone) derivatives with amino‐acid‐dependent groups

Baritaki¹,

Tzanakakis

Alifragis

et al. 2002

J. Biomed. Mater. Res.

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Two poly (vinyl pyrrolidone) (PVP) families with amino-acid residues (glycine, beta-alanine, gamma-aminobutiric acid and epsilon-aminocaproic acid) on the base of the co-polymer N-vinyl pyrrolidone and allyl-glycidyl ether (VP-AGE) and on the base of epoxidized PVP (EPVP) were synthesized. Static and dynamic light scattering measurements of these PVP derivatives in water showed that their structure/ behavior were similar to that of PVP. The bioreactivity was also similar to that of PVP. Further investigation of the immunoreactive properties of the derivatives in in vitro proliferation assays with fresh normal human peripheral blood lymphocytes and monocytes led to the determination of a costimulatory profile for each derivative in terms of polyclonal stimulation, specific antigen presentation, and immunoglobulin secretion. This profile allows the selection of an appropriate derivative as a carrier that would suit the immunoreactivity needs of the immobilized ligand.

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Section: Assessment Of the Co-polymer Reactivitymentioning

confidence: 80%

“…The isolated PBMC were treated with L-leucyl-L-leukine methyl ester hydro bromide (LLOMe) (Bachem Feinchemikalien AG, Budendorf, Switzerland), as previously described [8] to lyse lysosomerich cytolytic cells. 10 Monocytes were isolated from PBMC by selective adherence to the solid phase.…”

Section: Cellsmentioning

confidence: 99%

Light scattering and in vitro biocompatibility studies of poly (vinyl pyrrolidone) derivatives with amino‐acid‐dependent groups

Baritaki¹,

Tzanakakis

Alifragis

et al. 2002

J. Biomed. Mater. Res.

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“…The role of the in vitro stimulation also remains obscure as lymphocytes taken at 14 days and 4 months were stimulated by the same protocol. Recent reports of pretreating peripheral blood leucocytes with leucyl-leucine methyl ester prior to in vitro stimulation have shown that this is very important as it removes large granular lymphocytes, monocytes and a subset of (CDS/CD11 +) T cells, all implicated in suppression of antibody responses [2]. This antibody may be of use in screening other patients receiving IgG2b antibodies to see if Hib monoclonal antibody represents a predominant idiotype in patients injected with IgG2b antibody.…”

Section: Discussionmentioning

confidence: 96%

Production of a human monoclonal antibody recognising a determinant on mouse IgG2b from a patient receiving mouse monoclonal antibody for diagnostic imaging

Durrant

Robins

Ballantyne

et al. 1990

Cancer Immunol Immunother

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The development of human antibodies recognising mouse immunoglobulins represents an obstacle to effective antibody therapy. This study shows that patients produce modest titres of antibodies (predominantly anti-mouse rather than anti-idiotypic) after a single low-dose injection for immunoscintigraphy, suggesting that repeated imaging with the same or a different antibody could be a problem. Fusion of the lymphocytes from a patient who had been imaged twice previously resulted in a monoclonal antibody that specifically binds to an IgG2b isotypic determinant. Anti-IgG2b antibodies predominated in this patient's serum. Production of human monoclonal antibodies from patients given mouse monoclonal antibodies not only allows a finer dissection of the immune repertoire but also provides possible reagents for controlling the human anti-(mouse Ig) response, for selection of class-switch variants of mouse monoclonal antibodies and enhancing tumour imaging.

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“…This is toxic specifically for monocytes, NK cells and a subset ofT suppressor cells, that have been implicated in down-regulating antigen-specific activation of B cells [184]. The other group [180] had the relative advantage of starting with normal spleen cells and stimulated them with the adjuvant peptide MDP and a denatured preparation of HIV-1 prior to fusion with a human EBV transformant.…”

Section: In Vitro Immunizationmentioning

confidence: 99%

“…While the latter points are largely technical, the search for suitably immunized lymphocytes remains a major stumbling block, in particular for certain specificities in which highly immunized donors are unavailable. Advances in techniques for in vitro immunization will undoubtedly contribute to future studies, especially in the selection of lymphocyte subsets by Leu-Leu-OM e ester treatment [ 184] and in the use of appropriate cytokines. The production of HIV-specific hMoAbs, however, has its own peculiar difiSculties arising from both the effect that infection has on B lymphocytes in vivo and the immunosuppressive nature of some viral proteins.…”

Section: Human Moabsmentioning

confidence: 99%

B cell responses to HIV and the development of human monoclonal antibodies

Boyd

James

1992

Clinical and Experimental Immunology

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SUMMARYIn this review B cell responses in HIV-infected individuals are summarized together with the techniques used to date to produce human monoclonals to HIV and the properties of these antibodies. Profound disturbances in B cell responses are apparent both in vivo and in vitro. While there is evidence in vivo of marked polyclonal B cell activation, primary and secondary antibody responses are impaired. Similarly these cells exhibit spontaneous immunoglobulin secretion upon in vitro culture but do not readily respond to B cell mitogens and recall antigens including HIV. Furthermore, certain of these defects can be reproduced in normal B cells in vitro by incubation with HIV or HIV coded peptides. Individuals infected with HIV develop antibodies to HIV structural proteins (e.g. pl7, p24, gp41 and gpl20) and regulatory proteins (e.g. vif, nef, RT). Autoantibodies against a number of immunologically important molecules are also frequently observed. The anti-HIV antibodies are predominantly ofthe IgGl isotype and exhibit a variety of effects on the virus in vitro. To date, using conventional immortalization strategies, an appreciable number of human monoclonals to HIV have been developed. These have been specific for gp41, gpl20 and gag with antibodies ofthe former specificity predominating. The majority of these antibodies have been ofthe IgGl isotype. Only a small number ofthe antibodies neutralize virus in vitro and most of these react with gpl20. The neutralizing antibodies recognize conformational and carbohydrate epitopes or epitopes in amino acid positions 306-322. The predominant epitopes recognized by the anti-gp41 antibodies were in amino acid positions 579-620 and 644-662. A high percentage (=^ 25%) of these antibodies enhance viral growth in vitro. The problems relating to the production of human monoclonals to HIV are discussed together with strategies that could be used in the future.

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Strategy for the production of human monoclonal antibodies using in vitro activated B cells

Cited by 61 publications

References 26 publications

Light scattering and in vitro biocompatibility studies of poly (vinyl pyrrolidone) derivatives with amino‐acid‐dependent groups

Light scattering and in vitro biocompatibility studies of poly (vinyl pyrrolidone) derivatives with amino‐acid‐dependent groups

Production of a human monoclonal antibody recognising a determinant on mouse IgG2b from a patient receiving mouse monoclonal antibody for diagnostic imaging

B cell responses to HIV and the development of human monoclonal antibodies

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