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Traditional hybridoma and B cell cloning antibody discovery platforms have inherent limits in immune repertoire sampling depth. One consequence is that monoclonal antibody (mAb) leads often lack the necessary affinity for therapeutic applications, thus requiring labor-intensive and time-consuming affinity in vitro engineering optimization steps. Here, we show that high-affinity variants of mouse-derived mAbs can be rapidly obtained by testing of somatic sequence variants obtained by deep sequencing of antibody variable regions in immune repertories from immunized mice, even with a relatively sparse sampling of sequence variants from large sequence datasets. Affinity improvements can be achieved for mAbs with a wide range of affinities. The optimized antibody variants derived from immune repertoire mining have no detectable in vitro off-target binding and have in vivo clearance comparable to the parental mAbs, essential properties in therapeutic antibody leads. As generation of antibody variants in vitro is replaced by mining of variants generated in vivo, the procedure can be applied to rapidly identify affinity-optimized mAb variants.
This article was published in the following journal.
The adaptive immune response generates a large repertoire of T cells with T-cell receptors (TCR and TCR) and B cells with immunoglobulins (Ig). The repertoire changes in response to antigen stimulatio...
The engineering of antibodies and antibody fragments for affinity maturation, stability, and other biophysical characteristics is a common aspect of therapeutic development. Maturation of antibodies i...
B cell immunoglobulin (Ig) repertoire composition shapes immune responses. The generation of Ig diversity begins with Ig variable region exon assembly from gene segments, random inter-segment junction...
The therapeutic efficacy of an antibody drug depends on the variable domains and on the constant crystallizable fragment (Fc). IgG variable domains have been the targets of extensive molecular enginee...
Antibodies are considered the hallmark of the adaptive immune system in that they mediate various key biological functions, such as direct neutralization and recruitment of effector immune cells to el...
This study is designed to evaluate the untreated NSCLC patients. After participants have accepted chemotherapy, radiotherapy, and immunotherapy, the investigators used the next generation ...
This is an open label trial of mouse allergenic extract administered by subcutaneous injection in adults with asthma and mouse sensitivity. The study is designed to evaluate: - the saf...
To analyze the proportion of hereditary tumors in ovarian cancer patients in China, as well as the spectrum of variations; the ctDNA characteristics in patients with ovarian cancer; the co...
The broad objective of this study is to test the association between hyperoxia exposure after resuscitation from cardiac arrest and outcome. After obtaining written informed consent subjec...
This study was designed to evaluate the long term effectiveness of a product used in knee surgery called Affinity™ Membrane.
Semisynthetic conjugates of various toxic molecules, including RADIOACTIVE ISOTOPES and bacterial or plant toxins, with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; and ANTIGENS. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect.
Conditions characterized by the presence of M protein (Monoclonal protein) in serum or urine without clinical manifestations of plasma cell dyscrasia.
Anti-CD3 monoclonal antibody that exerts immunosuppressive effects by inducing peripheral T-cell depletion and modulation of the T-cell receptor complex (CD3/Ti). This biochemically purified IMMUNOGLOBULIN G is obtained through the fusion of mouse myeloma cells to lymphocytes from immunized animals to produce hybridomas that secrete specific antibodies to the T3 (CD3) antigens of human T-lymphocytes. It is often used as an IMMUNOSUPPRESSIVE AGENTS in TRANSPLANTATION.
An anti-IgE, recombinant, humanized monoclonal antibody which specifically binds to the C epsilon3 domain of IMMUNOGLOBULIN E, the site of high-affinity IgE receptor binding. It inhibits the binding of IgE to MAST CELLS and BASOPHILS to reduce the severity of the allergic response and is used in the management of persistent allergic ASTHMA.
A genus of the subfamily SIGMODONTINAE consisting of 49 species. Two of these are widely used in medical research. They are P. leucopus, or the white-footed mouse, and P. maniculatus, or the deer mouse.
Monoclonal antibodies MAbs
Monoclonal antibodies recognise and attach to specific proteins produced by cells. Types of monoclonal antibodies used to treat cancer cells: Block cell dividing dividing signals Transport cancer drugs or radiation to cancer cells Tr...
Hybridoma technology is a technology of forming hybrid cell lines (called hybridomas) by fusing an antibody-producing B cell with a myeloma (B cell cancer) cell that is selected for its ability to grow in tissue culture and for an absence of antibody cha...