Amplifying tumor recognition and drug susceptibility by multivalent ApDC assembly to combat with tumor cell...

Area of Science:

• Biotechnology
• Molecular Biology
• Oncology

Background:

• Molecular targeted therapies like antibody-drug conjugates (ADCs) show promise but face challenges due to tumor cell heterogeneity and low antigen expression.
• Bispecific and biparatopic antibodies offer alternative targeting strategies, yet their construction and synergistic effects remain complex.

Purpose of the Study:

• To develop a programmable method for constructing multivalent and multi-specific aptamer-drug conjugates (mApDCs).
• To enhance targeted therapy efficiency by improving tumor cell recognition, internalization, and cytotoxicity.
• To address limitations of current targeted therapies in combating tumor heterogeneity and weak antigen expression.

Main Methods:

• A programmable strategy was employed to assemble multivalent and multi-specific aptamer-drug conjugates (mApDCs).
• The efficacy of mApDCs was evaluated in terms of target-initiated tumor cell recognition, internalization, and cytotoxicity.
• In vivo studies assessed tumor accumulation, retention, and tumor growth inhibition in various tumor models.

Main Results:

• The developed mApDCs demonstrated amplified efficiency in tumor cell recognition, internalization, and cytotoxicity.
• Both multivalent and multi-specific mApDC patterns exhibited high specificity for targeted antigens.
• Enhanced tumor accumulation, prolonged retention, and significant tumor growth inhibition were observed across different tumor types.

Conclusions:

• This study presents a programmable strategy for developing advanced targeted therapies using mApDCs.
• The mApDC approach effectively combats tumor cell heterogeneity and overcomes resistance associated with weak tumor antigen expression.
• This platform offers a promising avenue for developing more effective cancer treatments.