Antibody engineering: facing new challenges in cancer therapy

Area of Science:

• Biotechnology
• Immunology
• Pharmacology

Background:

• Antibody-based therapeutics, once termed 'magic bullets', faced initial disappointment but are now achieving clinical and commercial success.
• Engineered antibodies constitute over 30% of biopharmaceuticals currently in clinical trials, highlighting their growing importance.

Purpose of the Study:

• To review the structure and mechanisms of action of various recombinant antibodies.
• To explore strategies for enhancing the efficacy of therapeutic antibodies.
• To discuss the advantages of gene therapy for in vivo antibody production.

Main Methods:

• Review of recent structural and functional data on antibody engineering.
• Analysis of strategies for enhancing antibody-mediated cytotoxicity (complement-mediated and antibody-dependent cellular cytotoxicity).
• Examination of methods for improving cytotoxic payloads (toxins, drugs, radionuclides, viral delivery).

Main Results:

• New generations of therapeutic antibodies have been designed using advanced structural and functional insights.
• Efficacy enhancement strategies include improved cytotoxicity mechanisms and targeted delivery of payloads.
• Gene therapy presents a promising approach for in vivo production of therapeutic antibodies, offering additional benefits.

Conclusions:

• Therapeutic antibodies have evolved significantly, with engineered versions demonstrating substantial clinical and commercial value.
• Diverse strategies are effectively increasing the potency and applicability of antibody-based therapies.
• In vivo antibody production via gene therapy represents a novel frontier in enhancing the therapeutic potential of antibodies.