About this Research Topic
Antibody-based strategies to cancer treatment have dramatically advanced in the last 30 years. In the 80s, hybridoma techniques enabled to produce monoclonal antibodies, and a dramatic efficacy of anti-idiotype antibodies to treat B cell lymphoma was reported. While 15 years passed, rituximab was approved as the first monoclonal antibody (mAb) for the treatment of cancer in 1997. Now, more than 20 mAbs have become standard of care for the treatment of both solid tumors and hematologic malignancies.
Most of the approved mAbs (e.g. rituximab, trastuzumab, cetuximab) target tumor-associated antigens on the surface of cancer cells and inhibit cell growth. Antibody dependent cell-mediated cytotoxicity (ADCC) is one of the primary mechanisms of anti-tumor activity of these antibodies, whereby Fc receptor bearing natural killer (NK) cells bind to the antibody-targeted tumor cell and mediate tumor cell lysis. Although several effective antibodies have emerged, long-term, durable responses remain elusive, and resistance and relapse remain major problems. Thus, the next generation of therapeutic antibodies are drug-conjugated antibodies to overcome cancer resistance. Antitumor antibodies can be used as vehicles for the selective delivery of cytotoxic agents to tumors. Trastuzumab conjugated to a maytansine derivative and brentuximab vedotin covalently modified with the microtubule antagonist monomethyl auristatin E showed good clinical efficacy and safety.
Immunomodulatory antibodies have revolutionized cancer immunotherapy. In 2011, the FDA approved the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)-specific mAb, ipilimumab, for the treatment of metastatic melanoma, representing a major milestone in cancer immunotherapy. The second FDA-approved immunomodulatory agent, pembrolizumab (anti-programmed cell death 1 (PD-1) mAb), was approved in 2014. Not only inhibitory antibodies to cancel the inhibitory immune system, but agonistic antibodies to accelerate the stimulatory immune system have been developed, and a huge number of attractive clinical trials are on-going. In addition, combination therapies of approved antibodies with chemotherapy, radiotherapy or other antibodies are in focus. It is anticipated that “Combination Cancer Immunotherapy” with therapeutic antibodies will make significant contributions to the field of cancer immunotherapy.
Recently, bioengineering has remarkably progressed. Modification of glycosylation in antibodies, e.g. afucosylated antibodies, can dramatically enhance ADCC. A novel bispecific antibody, blinatumomab, specific to CD19 and CD3, which can help to engage endogenous T cells to target malignant cells, was approved for patients with acute lymphoblastic leukemia. The bioengineering technologies to prolong a life-time of antibodies in the blood, to recycle antibodies in the body, to enhance the affinity for Fc receptor on NK cells, to initiate anti-cancer immune systems, to achieve the precision medicine have been launched. Innovative therapeutic antibodies and novel therapeutic strategies with antibodies are boosting cancer treatment.
The purpose of this Research Topic is to learn from the history of therapeutic antibodies and to provide insights into the challenge to overcome cancer with therapeutic antibodies. We will focus on contributions dealing with innovative technologies for therapeutic antibodies and the clinical promise of new therapeutic antibodies. We welcome all types of high quality articles to this Research Topic, including original research, reviews, and case reports.
Keywords: Cancer immune therapy, Bioengineering, Pharmacokinetics, Pharmacodynamics
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