Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since 1997, nine humanized antibodies received the approval of the FDA to be used as drugs for the treatment of various diseases including transplant rejections, metastatic breast and colon cancers, leukaemia, non-Hodgkin lymphomas, allergic conditions or multiple sclerosis. This review describes techniques used to engineer these antibodies and presents the recent evolutions of these techniques : SDRs grafting or << abbreviated >> CDRs grafting. Based on the illustrative examples of several antibodies, Mylotarg, Herceptin or Xolair, the therapeutic effectiveness of humanized antibodies are underlined and, with the example of Tysabri, the sometimes dramatic adverse effects associated with their clinical use is stressed. In a second part, this review presents some future and realistic avenues to improve the effectiveness of the humanized antibodies, to decrease their immunogenicity and to reduce their cost.
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PMID:[Humanized antibodies as therapeutics]. 1632 46

The introduction of monoclonal antibodies (MoAbs) into the treatment of cancer has led to improvements in patient survival. However, to the authors' knowledge, little attention has been paid to the infectious complications associated with their use. The authors performed a systematic review of the literature to identify randomized controlled trials (RCTs) that included in their outcomes a comparison of the infectious complications of a MoAb plus chemotherapy or radiotherapy versus the therapy regimen given without the addition of a MoAb. Twenty RCTs with relevant data regarding the use of MoAbs in patients with hematologic malignancies (10 RCTs) and solid tumors (10 RCTs) were retrieved. Six RCTs compared rituximab in conjunction with the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) versus CHOP alone for the treatment of B-cell non-Hodgkin lymphoma (NHL). No significant increase in the incidence of infections was observed with the addition of rituximab to chemotherapy (based on data from 5 RCTs). However, in patients who were seropositive for the human immunodeficiency virus (HIV), a 12% increase in infection-related deaths and a rate of higher opportunistic infections was associated with the rituximab-containing regimen (data taken from 1 RCT). Five RCTs either compared trastuzumab plus chemotherapy versus chemotherapy alone or trastuzumab monotherapy versus observation in patients with breast cancer. The addition of trastuzumab to the various chemotherapy regimens was found to cause a slight increase in the frequency of high-grade infections while bevacizumab caused a negligible increase in Grade III/IV infections compared with the same regimens given of chemotherapy alone. Based on a single trial, a higher comparable increase in the rate of high-grade infections was noted with the use of cetuximab in addition to chemotherapy compared with chemotherapy alone. MoAbs added to chemotherapy appear to have infectious complications that are comparable to the chemotherapy-alone regimen when administered for the treatment of NHL, with the exception of HIV-seropositive patients. Trastuzumab, which is reported to have a clear benefit in the prognosis of breast cancer patients, was found to cause a small increase in Grade III/IV infectious complications; however, there was no apparent difference in the rate of infection-related death.
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PMID:Infectious complications of monoclonal antibodies used in cancer therapy: a systematic review of the evidence from randomized controlled trials. 1742 39

The antibody-drug conjugate field has made significant progress recently owing to careful optimization of several parameters, including mAb specificity, drug potency, linker technology, and the stoichiometry and placement of conjugated drugs. The underlying reason for this has been obtained in pre-clinical biodistribution and pharmacokinetics studies showing that targeted delivery leads to high intratumoral free drug concentrations, while non-target tissues are largely spared from chemotherapeutic exposure. Recent developments in the field have led to an increase in the number of ADCs being tested clinically, with 3 in late stage clinical trials: brentuximab vedotin (also referred to as SGN-35) for Hodgkin lymphoma; Trastuzumab-DM1 for breast cancer; and Inotuzumab ozogamicin for non-Hodgkin lymphoma. This review highlights the recent pre-clinical and clinical advances that have been made.
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PMID:Antibody-drug conjugates: targeted drug delivery for cancer. 2064 72

The use of antibody drug conjugates (ADCs) as targeted chemotherapies has successfully entered clinical practice and holds great promise. ADCs consist of an antibody and toxin-drug combined together via a chemical linker. While the antibody and drug are of vital importance in the direct elimination of cancer cells, more advanced linker technology was instrumental in the delivery of more potent drugs with fewer side effects. Here, we discuss the preclinical experience as well as clinical trials, with a specific emphasis on the clinical outcomes and side effects, in addition to linker strategies for five different ADCs, in order to describe different approaches in the development of this new class of anticancer agents. Brentuximab vedotin is approved for use in Hodgkin's lymphoma and Trastuzumab emtansine is approved for breast cancer. Combotox, Inotuzumab Ozogamicin, and Moxetumomab Pasudotox are in various stages of clinical development and are showing significant efficacy in lymphoid malignancies. These ADCs illustrate the promise and future potential of targeted therapy for presently incurable malignancies.
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PMID:Linked-in: design and efficacy of antibody drug conjugates in oncology. 2365 30