Antibody-Drug Conjugates: The New Frontier of Chemotherapy

Abstract

In recent years, antibody-drug conjugates (ADCs) have become promising antitumor agents to be used as one of the tools in personalized cancer medicine. ADCs are comprised of a drug with cytotoxic activity cross-linked to a monoclonal antibody, targeting antigens expressed at higher levels on tumor cells than on normal cells. By providing a selective targeting mechanism for cytotoxic drugs, ADCs improve the therapeutic index in clinical practice. In this review, the chemistry of ADC linker conjugation together with strategies adopted to improve antibody tolerability (by reducing antigenicity) are examined, with particular attention to ADCs approved by the regulatory agencies (the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA)) for treating cancer patients. Recent developments in engineering Immunoglobulin (Ig) genes and antibody humanization have greatly reduced some of the problems of the first generation of ADCs, beset by problems, such as random coupling of the payload and immunogenicity of the antibody. ADC development and clinical use is a fast, evolving area, and will likely prove an important modality for the treatment of cancer in the near future.

Photoinduced Photosensitizer–Antibody Conjugates Kill HIV Env-Expressing Cells, Also Inactivating HIV

“…Previously, two generations of PICs were produced: homogeneous porphyrin-7B2 with a constant drug–antibody ratio (DAR) of 4 and heterogeneous IR700-PICs with different DARs of 2, 3, and 4. 19 Herein, the effects of light irradiation on the PICs were studied, physically and immunologically, using microcapillary electrophoresis, dynamic light scattering (DLS), and ELISA. Both porphyrin-7B2 and IR700-7B2 were irradiated equally by a custom-made LED device with a broad spectrum of light (380–780 nm).…”

“…Both porphyrin-7B2 and IR700-7B2 were irradiated equally by a custom-made LED device with a broad spectrum of light (380–780 nm). 19 …”

Marine Anticancer Agents: An Overview with a Particular Focus on Their Chemical Classes

“…More importantly, auristatins appeared as great payloads in antibody-drug conjugates (ADCs) [132]. The efficacy of ADCs to exploit antibodies to target specific molecules on tumor cells and selectively deliver otherwise highly toxic molecules [133] is evident by the fact that four compounds belonging to this class have recently been approved for the treatment of patients with cancer (Table 1) and over 20 other compounds are in clinical evaluation [134][135][136].…”

EV20/NMS-P945, a Novel Thienoindole Based Antibody-Drug Conjugate Targeting HER-3 for Solid Tumors

“…In recent years, antibody–drug conjugates (ADCs) have become promising antitumor agents in the context of personalized medicine [ 1 , 2 ]. These therapeutics are developed through the conjugation of antibodies to highly potent cytotoxic drugs.…”