To enable antibodies to function as cytotoxic anticancer agents, they are modified either via attachment to protein toxins or highly potent, low-molecular-weight drugs. Such molecules, termed immunotoxins and antibody-drug conjugates, respectively, represent a second revolution in antibody-mediated cancer therapy. Thus, highly toxic compounds are delivered to the interior of cancer cells based on antibody specificity for cell-surface target antigens.

http://cancerres.aacrjournals.org/content/canres/71/20/6300.full.pdf

Treatment of Hematologic Malignancies with Immunotoxins and Antibody-Drug Conjugates

One approach to improving activity of anticancer drugs is to conjugate them to antibodies that recognize tumor-associated, cell-surface antigens. The antibody-drug conjugate concept evolved following major advances, first, in the development of humanized and fully human antibodies; second, in the discoveries of highly cytotoxic compounds ('drugs) linkable to antibodies; and finally, in the optimization of linkers that couple the drug to the antibody and provide sufficient stability of the antibody-drug conjugate in the circulation, optimal activation of the drug in the tumor, and the ability of the activated drug to overcome multidrug resistance. In this article, we will review the considerations for selecting a target antigen, the design of the conjugate, and the pre-clinical and clinical experiences with the current generation of antibody-drug conjugates.

https://www.future-science.com/doi/pdf/10.4155/tde.10.98

Antibody-drug conjugates: using monoclonal antibodies for delivery of cytotoxic payloads to cancer cells.

Importance of the field: The number of disease-associated protein targets has significantly increased over the past decade due to advances in molecular and cellular biology technologies, human genetic mapping efforts and information gathered from the human genome project. The identification of gene products that appear to be involved in supporting the underlying cause of disease has offered the biopharmaceutical industry an opportunity to develop compounds that can specifically target these molecules to improve therapeutic responses and lower the risk of unwanted side effects that are commonly seen in traditional small chemical-based medicines.Areas covered in this review: An overview of targeted drug therapies is presented in this review. We include a review of the various classes of targeted therapeutic agents, the types of disease-associated molecules being targeted by these agents and the challenges currently being encountered for the successful development of these various platforms for the treatment...

Advances in targeted therapeutic agents

Antibody–drug conjugates (ADCs) for tumor therapy contain a cytotoxic drug conjugated to a monoclonal antibody (mAb) across a linker. A homing device, the mAb enables the recognition of tumor cells by binding to tumor-specific antigens. The linker is usually cleaved inside the tumor cell or close to the cell surface according to a well-designed chemical mechanism or upon in vivo degradation of the immunoglobulin moiety. The potent drug load is then released exerting its cytotoxic activity within the target cell or in its close proximity (bystander effect). This concept enables a highly selective approach to minimize side effects for the patient. In August 2011, Seattle Genetics’ ADC Adcetris® (brentuximab vedotin) was approved by the US FDA. This review gives background information on this interesting new technology and presents the relevant, recent patents in this research area. patents by Seattle Genetics, Immunogen and Biotest are discussed owing to their eminent contribution and relevance to the field.

Antibody-drug conjugates in tumor therapy.

Disclosed are methods and treatment regimes that include the administration of immunconjugates targeting CD138 to combat diseases. The immunoconjugate is either used as the sole active ingredient, as part of a treatment regime or as part of an anticancer combination.

Uses of immunoconjugates targeting CD138

The Monoclonal Antibody nBT062 Conjugated to Cytotoxic Maytansinoids Has Potent and Selective Cytotoxicity against CD138 Positive Multiple Myeloma Cells in Vitro and in Vivo.

Diana Cristia

Papers

The Monoclonal Antibody nBT062 Conjugated to Cytotoxic Maytansinoids Has Potent and Selective Cytotoxicity against CD138 Positive Multiple Myeloma Cells in Vitro and in Vivo.