Next generation of antibody therapy for cancer

Abstract

Monoclonal antibodies (mAbs) have become a major class of therapeutic agents providing effective alternatives to treating various human diseases. To date, 15 mAbs have been approved by regulatory agencies in the world for clinical use in oncology indications. The selectivity and specificity, the unique pharmacokinetics, and the ability to engage and activate the host immune system differentiate these biologics from traditional small molecule anticancer drugs. mAb-based regimens have brought clinical benefits, including improvements in overall survival, to patients with a variety of cancers. Many challenges still remain, however, to fully realize the potential of these new medicines. With our further understanding of cancer biology, mechanism of antibody action, and advancement of antibody engineering technologies, many novel antibody formats or antibody-derived molecules are emerging as promising new generation therapeutics. Carefully designed and engineered, they retain the advantage of specificity and selectivity of original antibodies, but in the meantime acquire additional special features such as improved pharmacokinetics, increased selectivity, and enhanced anticancer efficacy. Promising clinical results are being generated with these newly improved antibody-based therapeutics.

Conceptual Evolution of Cell Signaling

“…Monoclonal antibodies (mAb) against IGF-1R like Cixutumumab, Figitumumab, Dalotuzumab, R1507, and Ganitumab are in different phases of clinical trials [191]. Trastuzumab, an mAb, which blocks HER2 overexpressed in invasive breast cancers underwent two axial trails in patients with metastatic breast cancer [192]. In the treatment of metastatic colon cancer, Bevacizumab in combination with irinotecan, fluorouracil, and leucovorin that acts on VEGFA (angiogenesis pathway), gained the approval of FDA as the first systemic anti-angiogenic drug [193].…”

The role of IgE specific for galactose-α-1,3-galactose in predicting cetuximab induced hypersensitivity reaction: a systematic review and a diagnostic meta-analysis

“…Recombinant monoclonal antibodies are currently used in the treatment of various diseases, from asthma, rheumatoid arthritis and inflammatory bowel disease to cancer 1 , 2 . Bevacizumab, panitumumab, trastuzumab, rituximab, cetuximab represent a new generation of molecules that are being used to treat different types of malignancies 3 – 6 . Although monoclonal antibodies are known to have fewer toxic reactions compared to the conventional cytotoxic antineoplastic drugs, several cases of severe systemic hypersensitivity reaction (HSR) have been reported 4 , 7 – 10 .…”

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“…What makes breast cancer so lethal is its propensity to metastasize, preferentially to lymph nodes, lung and bone [5]; less toxic and more effective chemopreventive and anti-metastatic treatments are desperately required if there is to be any advancement in reducing both mortality and morbidity. Because natural antibodies have higher target specificity, lower systemic toxicity, and longer half-life [6], there is increasing interest in the therapeutic aspect of antigen-antibody interaction.…”