Perspectives on the development of antibody-drug conjugates targeting ROR1 for hematological and solid cancers

Area of Science:

• Oncology
• Pharmacology
• Biotechnology

Background:

• Antibody-drug conjugates (ADCs) represent a significant advancement in targeted cancer therapy, offering improved therapeutic indexes over traditional chemotherapy.
• The development of ADCs involves the conjugation of cytotoxic payloads to monoclonal antibodies (mAbs) for selective delivery to antigen-positive cancer cells.
• Ten ADCs have received FDA approval, with approximately 80 more in clinical trials for various hematological and solid malignancies.

Purpose of the Study:

• To review the design and development of current anti-ROR1 ADCs.
• To highlight the emerging trend of targeting ROR1 for cancer therapy.
• To discuss the critical role of ADC components (antibody, linker, payload, conjugation method) in therapeutic efficacy.

Main Methods:

• Review of existing literature on antibody-drug conjugates.
• Analysis of ADCs targeting receptor tyrosine kinase like orphan receptor 1 (ROR1).
• Examination of ADC component selection and their impact on performance.

Main Results:

• Receptor tyrosine kinase like orphan receptor 1 (ROR1) has emerged as a highly attractive target for cancer therapy.
• Three ADCs targeting ROR1 gained significant attention in late 2020, being acquired or licensed by major pharmaceutical companies.
• The choice and combination of antibody, linker, payload, and conjugation method are crucial for ADC efficacy.

Conclusions:

• Targeting ROR1 with ADCs is a rapidly developing area in cancer therapeutics.
• The strategic design of ADC components is essential for advancing ROR1-targeted therapies.
• ROR1-targeted ADCs show considerable promise for treating both hematological and solid tumors.