Reshaping human antibodies for therapy

@article{Riechmann1988ReshapingHA,
  title={Reshaping human antibodies for therapy},
  author={Lutz Riechmann and Michael Ronald Clark and Herman Waldmann and Gregory Paul Winter},
  journal={Nature},
  year={1988},
  volume={332},
  pages={323-327}
}
A human IgGI antibody has been reshaped for serotherapy in humans by introducing the six hypervariable regions from the heavy- and light-chain variable domains of a rat antibody directed against human lymphocytes. The reshaped human antibody is as effective as the rat antibody in complement and is more effective in cell-mediated lysis of human lymphocytes. 
View on Nature
nature.com
1,577 Citations
Highly Influential Citations
27
Background Citations
315
Methods Citations
56
Results Citations
3

1,577 Citations

Reshaping a Human Monoclonal Antibody to Inhibit Human Respiratory Syncytial Virus Infection in Vivo
TLDR
This second generation reshaped human monoclonal antibody cross-reacted with all clinical isolates of RSV tested and both prevented disease and cured mice even when administered four days after infection.
A humanized antibody against human cytomegalovirus (CMV) gpUL75 (gH) for prophylaxis or treatment of CMV infections.
TLDR
A humanized monoclonal antibody that binds to the 86-kDa glycoprotein, gpUL75 (gH), of human cytomegalovirus (CMV) has been developed and provides a potential agent for the prevention or treatment of CMV infections in humans.
Humanisation of monoclonal antibodies for therapy.
TLDR
Encouraging preliminary results have been obtained and it seems likely that these will dictate the use of humanisation as a required procedure in the therapeutic use of monoclonal antibodies.
Anti-globulin responses to rat and humanized CAMPATH-1 monoclonal antibody used to treat transplant rejection.
TLDR
Although anti-idiotype responses are theoretically possible against humanized therapeutic antibodies and are especially likely to be provoked by cell-binding antibodies, these data show that humanization offers a significant reduction in immunogenicity, potentially allowing repeat courses of treatment.
“Primatization” of Recombinant Antibodies for Immunotherapy of Human Diseases: A Macaque/Human Chimeric Antibody Against Human CD4
TLDR
It is shown that cynomolgus macaques are phylogenetically distant enough to respond against conserved human antigens, and a human/monkey chimeric anti-CD4 antibody with an apparent affinity of 3.2 × 10−11 M and exhibits potent immunosuppressive properties in vitro.
CDR Repair: A Novel Approach to Antibody Humanization
TLDR
This data indicates that the production of a human anti-mouse antibody (HAMA) response in patients despite the high degree of sequence similarity shared between human and mouse antibodies through the construction of chimeras is likely to be a cause for concern.
Reshaping a human antibody to inhibit the interleukin 6-dependent tumor cell growth.
TLDR
The reshaped human PM-1 antibody, consisting of human REI-based light chain and NEW-based heavy chain variable regions, could be efficacious in human multiple myeloma patients.
A humanized monovalent CD3 antibody which can activate homologous complement
TLDR
Comparison of the mono‐ and bivalent humanized mAb in a complement‐mediated cell lysis assay revealed that the monovalent antibody mediated lysis of human T cell blasts whereas the bivalent form did not.
ANTIBODES BINDING TO ATHERAPEUTIC MONOCLONAL ANTIBODY
  • Biology
  • 2017
TLDR
Methods and systems for the determination of antigen specific antibodies of a par ticular immunoglobulin class and for the identification of a patient who is at risk of developing an adverse drug reaction (ADR) during treatment with a TmAB are outlined.
Development and Clinical Experience with Humanised Monoclonal Antibodies
TLDR
A reshaped human antibody with the same specificity was constructed by genetic engineering and it is believed that this antibody will be a potent immunosuppressant as well as being useful as a component of therapy for lymphoid malignancies.
...
...

References

SHOWING 1-10 OF 36 REFERENCES
Tolerance to rat monoclonal antibodies. Implications for serotherapy
TLDR
It is shown that it is possible to induce tolerance in mice to the constant regions of rat IgG2b mAbs by both classical deaggregation methods and by anti-L3T4 mAb therapy, suggesting that the use of human or chimeric mAbs will not be sufficient to eliminate the antiglobulin response, and that additional methods need to be investigated.
Biological and clinical implications of lymphocyte hybridomas: tumor therapy with monoclonal antibodies.
TLDR
Preliminary studies show that problems such as antigenic modulation, circulating free antigen, effector cell shortage, and host anti-mouse immunoglobulin response must be overcome.
Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies
TLDR
The results suggest that IgG1 might be the favoured IgG subclass for therapeutic applications in complement-dependent hemolysis and in antibody-dependent cell-mediated cytotoxicity using both human effector and human target cells.
Idiotype switching of CD4‐specific monoclonal antibodies can prolong the therapeutic effectiveness in spite of host anti‐mouse IgG antibodies
TLDR
The feasibility of idiotype switching of therapeutic mAb to evade this anti‐idiotype response is demonstrated and prolongation of the therapeutic effectiveness of mAb treatment can be achieved.
Production of functional chimaeric mouse/human antibody
The availability of monoclonal antibodies has revived interest in immunotherapy. The ability to influence an individual's immune state by administering immunoglobulin of the appropriate specificity…
Monoclonal antibody therapeutic trials in seven patients with T-cell lymphoma
TLDR
Four patients developed anti-mouse immunoglobulin (Ig) antibodies, and in three patients, this was responsible for tumor escape from therapy, and a small but significant component was found to be antiidiotype.
Chimeric mouse-human IgG1 antibody that can mediate lysis of cancer cells.
TLDR
The chimeric antibody, but not the mouse L6 antibody, is effective against a melanoma line expressing small amounts of the L6 antigen, and points to the usefulness of the chimeric antibodies approach for obtaining agents with strong antitumor activity for possible therapeutic use in man.
A hapten-specific chimaeric IgE antibody with human physiological effector function
TLDR
The emergence of techniques allowing the stable introduction of immunoglobulin gene DNA into myeloma cells3–5 has allowed us to construct a mouse cell line that secretes a chimaeric IgE, λ1 antibody whose heavy chain is composed of a human Cε constant region fused to a mouse variable (VH) region.
Isolation of low-frequency class-switch variants from rat hybrid myelomas.
Characterization of a mouse/human chimeric monoclonal antibody (17-1A) to a colon cancer tumor-associated antigen.
TLDR
This human/mouse chimeric monoclonal antibody may be a good candidate for use in clinical trials because it retains the tumor antigen specificity and human effector cell recognition of the native 17-1A, would presumably have a fivefold to 10-fold longer circulating half-life in man, and should be considerably less immunogenic as compared with native murine immunoglobulins.
...
...