Human monoclonal antibodies produced by primary in vitro immunization of peripheral blood lymphocytes.

Borrebaeck, Carl; Danielsson, Lena; Möller, Susanna A.

doi:10.1073/pnas.85.11.3995

Cited by 96 publications

(43 citation statements)

References 31 publications

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“…An alternative possibility is that HMFG1 murine monoclonal antibody when administered intraperitoneally into humans, can cause a cascade of immunological reactions leading to humoral (Courtenay-Luck et al, 1988;Herlyn et al, 1991) and cellular (Kosmas et al, 1991) activation of the immune system with resultant antitumour effects. If this is the cause of the observed prolongation of survival in patients with ovarian cancer in this study, then, ironically, the use of murine monoclonal antibodies may be more effective than the recently described chimeric (LoBuglio et al, 1989), humanised (Reichmann et al, 1988) or completely human (Borrebaeck et al, 1988) monoclonal antibodies.…”

Section: Discussionmentioning

confidence: 99%

Adjuvant therapy of ovarian cancer with radioactive monoclonal antibody

Hird

Maraveyas²,

Snook³

et al. 1993

Br J Cancer

144

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Fifty-two patients with epithelial ovarian cancer were treated with yttrium-90-labelled monoclonal antibody HMFG1 administered intraperitoneally following conventional surgery and chemotherapy as part of an extended phase I-II trial. The treatment was well tolerated and the only significant toxicity observed was reversible myelosuppression as previously described. Following conventional surgery and chemotherapy, 21 out of the 52 patients had no evidence of residual disease and were regarded as receiving treatment in an adjuvant setting. To date, two of these patients have died of their disease (follow-up 3-62 months, median follow-up 35 months). This extended phase I-II study suggests that patients with advanced ovarian cancer who achieve a complete remission following conventional therapy may benefit from further treatment with intraperitoneal radioactive monoclonal antibody.

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Section: Discussionmentioning

confidence: 99%

Adjuvant therapy of ovarian cancer with radioactive monoclonal antibody

Hird

Maraveyas²,

Snook³

et al. 1993

Br J Cancer

144

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“…CAMPATH-1, a CDR graft of anti-lymphoma monoclonal antibody has been very successful in the therapy of non-Hodgkin's lymphoma and rheumatoid arthritis (123)(124)(125). Borrebaeck et al (126) described an in vitro method for immunization that produces human-human hybridoma secreted monoclonal antibodies specific for digoxin, haemocyanine and one recombinant fragment of gp120 envelope glycoprotein of HIV. Recent developments in humanized antibodies have been reviewed by Winter and Harris (114).…”

Section: Second Generation Antibodiesmentioning

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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“…(32'33) When actively immunized human donors are not available, spleen, bone marrow, and/or lymph node tissue should be used whenever ethically possible because the number of activated B cells will be low in the peripheral blood. If peripheral blood from human donors not actively immunized must be used, then the frequency of antigen-specific clones may be increased by in vitro immunization (34) or by including IgM Fd sequences in the Fab gene cassette, which are typically polyreactive and of lower affinity. (z9)…”

Section: Preparation Of B-cell Cdnamentioning

confidence: 99%

Construction of phagemid display libraries with PCR-amplified immunoglobulin sequences.

Hogrefe¹,

Shopes²

1994

Genome Research

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The expression of active antibody fragments in Escherichia coli has led to significant advances in the identification of antigen-binding clones using molecular biological techniques. (1-7) When coupled with the recently developed phage display technology, (8'0) Fab fragment libraries containing up to 10 8 unique specificities may be readily constructed and screened. Using the phage display screening technique, clones that bind to a particular antigen may be isolated by enriching (biopanning) libraries of recombinant phagemid that display Fab on the surface as a fusion with the minor coat protein cpIII of M13. (1~ The phagemid contain the light-chain and heavychain genes of the displayed Fab, thereby allowing further characterization and manipulation of antigen-binding activity at the molecular level. (ls-2o) The diversity of the immunoglobulin repertoire may be effectively captured by PCR. Light-and heavy-chain genes are amplified by PCR from reverse-transcribed transcripts of the rearranged immunoglobulin genes. To construct comprehensive Fab libraries, exhaustive sets of PCR primers have been designed by us (1~ this article) and others (3' 17,21-26) that correspond to the amino terminus of the variable regions of known immunoglobulins and the carboxyl terminus of the CH1 domains of the heavy-chain isotypes or the K and k light chains.A number of strategies have been devised to recombine diverse repertoires of light-and heavy-chain sequences randomly into a bicistronic operon expressing Fab. These include sequential cloning, (12) PCR with a linker primer, (17) splice overlap extension, (27) ligating together two restriction-digested vectors, each encoding a single chain (6'7) and, finally, ligating the light-and heavy-chain Fd sequences together at a rare nonpalindromic restriction site. (1~ The latter approach represents an efficient, one-step cloning method that avoids potential unnecessary skewing of the immunoglobulin repertoire. With combinatorial approaches, it has been possible to construct Fab libraries containing up to 10 8 unique clones, the limiting factor being transformation of bacteria by plasmid or by infection. Methodologies for constructing larger libraries on the theoretical scale of 1012 clones are currently under development and may permit isolation of rare specificities with high affinity without the necessity of prior immunization. MATERIALS AND METHODS StrategyWe have developed a simplified, but efficient, method for constructing comprehensive phage display libraries of human Fab fragments (Fig. 1). A schematic of the SurfZAP lambda vector (Stratagene Cloning Systems) (1~ with a Fab gene cassette is shown in Figure 2. In our Fab fragment library constructs, the heavy-chain Fd portion (VH-D-J-CH1 domains) is expressed as a fusion with the M13 minor coat protein cpIII, although light-chain-cpIII fusions have been used successfully by others. (16) The light-chain and Fd-cpIII sequences are transcribed as a polycistronic message from the lacZ promoter.The SurfZAP vector encodes a ribosome-b...

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Human monoclonal antibodies produced by primary in vitro immunization of peripheral blood lymphocytes.

Cited by 96 publications

References 31 publications

Adjuvant therapy of ovarian cancer with radioactive monoclonal antibody

Adjuvant therapy of ovarian cancer with radioactive monoclonal antibody

Monoclonal antibodies in drug targeting

Construction of phagemid display libraries with PCR-amplified immunoglobulin sequences.

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