Trastuzumab emtansine: a novel antibody-drug conjugate for HER2-positive breast cancer.
Summary of "Trastuzumab emtansine: a novel antibody-drug conjugate for HER2-positive breast cancer."
Introduction: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) that combines intracellular delivery of the potent cytotoxic agent, DM1 (a derivative of maytansine) with the antitumor activity of trastuzumab. While there are several ADCs in Phase III development, T-DM1 is the only one in which the targeting antibody has antitumor properties. T-DM1 is also the only ADC that is directed toward the human EGFR 2 (HER2). Effective therapies are limited in HER2-positive advanced or metastatic breast cancer (MBC), particularly following progression on available HER2-targeted therapies. Areas covered: The mechanisms of action, preclinical efficacy and clinical profile of T-DM1 are reported. The latest preclinical and clinical data for T-DM1 are examined. Expert opinion: T-DM1 has significant antitumor potency in vitro and in vivo, which is maintained in tumors resistant to trastuzumab or lapatinib. In Phase I and II trials, T-DM1 provided objective tumor responses and was well tolerated across various lines of therapy in patients with HER2-positive MBC. In addition, it showed similar efficacy to trastuzumab plus docetaxel in first-line MBC. Ongoing trials (including two Phase III studies) are investigating T-DM1 as single-agent therapy or combined with other chemotherapeutic or biologic agents, and the results should help to define the place of T-DM1 within current treatment algorithms for HER2-positive disease.
Drug Development, Sarah Cannon Research Institute , 250 25th Avenue North, Suite 110, Nashville, TN 37203-1632 , USA +1 615 329 7274 ; +1 615 340 1576 ; email@example.com.
This article was published in the following journal.
Name: Expert opinion on biological therapy
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21506905
- DOI: http://dx.doi.org/10.1517/14712598.2011.580273
Medical and Biotech [MESH] Definitions
Semisynthetic vaccines consisting of polysaccharide antigens from microorganisms attached to protein carrier molecules. The carrier protein is recognized by macrophages and T-cells thus enhancing immunity. Conjugate vaccines induce antibody formation in people not responsive to polysaccharide alone, induce higher levels of antibody, and show a booster response on repeated injection.
Fluorescent Treponemal Antibody-absorption Test
Serologic assay that detects antibodies to Treponema pallidum, the etiologic agent of syphilis. After diluting the patient's serum to remove non-specific antibodies, the serum is mixed on a glass slide with Nichol's strain of Treponema pallidum. An antigen-antibody reaction occurs if the test is positive and the bound antibodies are detected with fluoresceinated antihuman gamma-globulin antibody.
The phenomenon of immense variability characteristic of ANTIBODIES. It enables the IMMUNE SYSTEM to react specifically against the essentially unlimited kinds of ANTIGENS it encounters. Antibody diversity is accounted for by three main theories: (1) the Germ Line Theory, which holds that each antibody-producing cell has genes coding for all possible antibody specificities, but expresses only the one stimulated by antigen; (2) the Somatic Mutation Theory, which holds that antibody-producing cells contain only a few genes, which produce antibody diversity by mutation; and (3) the Gene Rearrangement Theory, which holds that antibody diversity is generated by the rearrangement of IMMUNOGLOBULIN VARIABLE REGION gene segments during the differentiation of the ANTIBODY-PRODUCING CELLS.
Fluorescent Antibody Technique
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes.
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