Human Antibodies from Transgenic Mice

Lönberg, Nils

doi:10.1002/9780470485408.ch5

Cited by 6 publications

(7 citation statements)

References 199 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fully human antibodies are also being generated in transgenic mice expressing human Ig repertoire [Green et al, 1994;Lonberg and Huszar, 1995;Lonberg et al, 1994]. In these ''humanized'' mice, the endogenous mouse Ig genes are deleted and replaced with their human counterparts.…”

Section: Antibody Discovery and Engineeringmentioning

confidence: 99%

“…Since the mid-1990s, with the availability of human antibody phage display libraries [McCafferty et al, 1990;Clackson et al, 1991;Winter et al, 1994] and human Ig transgenic mice [Green et al, 1994;Lonberg et al, 1994;Lonberg and Huszar, 1995], fully human antibodies with desired specificities can now be readily isolated. Phage display technique, by linking the phenotype (antibody fragments) and the genotype (DNA encoding the corresponding antibody fragments) together in a phage particle, mimics the in vivo antibody response and selection process in vitro.…”

Section: Antibody Discovery and Engineeringmentioning

confidence: 99%

See 1 more Smart Citation

Development of antibody-based therapeutics for oncology indications

Li¹,

Zhu²

2006

Drug Dev. Res.

View full text Add to dashboard Cite

Monoclonal antibodies have emerged as novel oncology therapeutics. These biologics exert anticancer effects via a variety of mechanisms of action including modulating the function of key regulatory molecules and signaling pathways of tumor cells such as blocking growth factor/receptor interaction and/or down-regulating expression of oncogenic proteins (e.g., growth factor receptors) on the cell surface; recruiting effector mechanisms of the immune system, such as antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity; as a targeting device in immnuoconjugates; and other mechanisms such as anti-idiotype, catalytic antibodies, or antibodies that modulate patient's immune responses to tumors. In this review, we focus on the research and development experience of four such representative antibody therapeutics, rituximab (Rituxan s ), trastuzumab (Herceptin s ), cetuximab (Erbitux s ), and bevacizumab (Avastin s ), approved for treating non-Hodgkin's lymphoma, metastatic breast cancer, and colorectal cancer, respectively. The biology behind each antibody target, their proposed mechanisms of action, as well as preclinical and clinical development of these antibodies are the topics of this article. Experience drawn from the development process of these four antibodies is instrumental for ongoing and future antibody development activities. In addition, perspective views on challenges and opportunities of oncology antibody therapeutics are presented. Drug Dev. Res. 67: 699-728, 2006.

show abstract

Section: Antibody Discovery and Engineeringmentioning

confidence: 99%

Section: Antibody Discovery and Engineeringmentioning

confidence: 99%

Development of antibody-based therapeutics for oncology indications

Li¹,

Zhu²

2006

Drug Dev. Res.

View full text Add to dashboard Cite

show abstract

“…Although partially humanized antibodies have demonstrated significantly reduced immunogenicity, the most desirable antibodies for therapeutic applications in humans would be fully humanized antibodies [57]. Transgenic mice have been constructed which have had their own immunoglobulin genes functionally replaced with human immunoglobulin genes so that they produce human antibodies upon immunization [58-60]. Elimination of mouse antibody production was achieved by inactivation of mouse Ig genes in the ES cells by using gene-targeting technology to delete crucial cis -acting sequences involved in the process of mouse Ig gene rearrangement and expression.…”

Section: Applications Of Gene Targeting In Domestic Animalsmentioning

confidence: 99%

Specific genetic modifications of domestic animals by gene targeting and animal cloning

Wang¹,

Zhou²

2003

Reprod Biol Endocrinol

View full text Add to dashboard Cite

The technology of gene targeting through homologous recombination has been extremely useful for elucidating gene functions in mice. The application of this technology was thought impossible in the large livestock species until the successful creation of the first mammalian clone "Dolly" the sheep. The combination of the technologies for gene targeting of somatic cells with those of animal cloning made it possible to introduce specific genetic mutations into domestic animals. In this review, the principles of gene targeting in somatic cells and the challenges of nuclear transfer using gene-targeted cells are discussed. The relevance of gene targeting in domestic animals for applications in bio-medicine and agriculture are also examined.

show abstract

“…Another possibility is to utilise transgenic mice whose loci coding antibodies have been replaced by their human counterparts. With these mice, human antibodies can be generated by hybridoma technology but these transgenic animals are available in a very limited number of laboratories only (Fishwild et al, 1996;Jakobovits, 1995;Lonberg and Huszar, 1995;Nelson et al, 2010). For the isolation of antibodies directed against toxins, animals are immunised by non-toxic subunits or even selected domains from these subunits (Pelat et al, 2009a;Pelat et al, 2007;Scotcher et al, 2010;Winterroth et al, 2010).…”

Section: Antibody Phage Displaymentioning

confidence: 99%