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Accum™ Technology: A Novel Conjugable Primer for Onco-Immunotherapy
Abed El-Hakim El-Kadiry1, Simon Beaudoin2, Sebastien Plouffe2
1Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC H3T 1J4, Canada.
Molecules (Basel, Switzerland)
|June 24, 2022
Summary
Accum™ enhances biologic delivery by facilitating endosome escape and nuclear targeting. This improves antibody-drug conjugate (ADC) cancer cell killing and boosts anti-cancer immune responses for tumor antigens.
Area of Science:
- Biotechnology and Drug Delivery
- Onco-immunotherapy
- Cellular Trafficking Mechanisms
Background:
- Biologics often have compromised activity due to inefficient endosome trafficking into target cells.
- In cancer cells, antibody-drug conjugates (ADCs) are trapped in endosomes or effluxed, reducing intracellular accumulation and efficacy.
- Antigens in dendritic cells (DCs) face proteolysis within endosomes, diminishing immunogenicity before presentation.
Purpose of the Study:
- To develop a novel biotechnology, Accum™, to overcome endosomal entrapment and enhance biologic delivery.
- To enable endosome escape and prompt nuclear targeting for improved intracellular accumulation and functionalization of coupled biologics.
- To validate Accum™'s efficacy with antibody-drug conjugates (ADCs) and tumor antigens in cancer settings.
Main Methods:
- Biochemical characterization of Accum™, a conjugable biotechnology incorporating cholic acid (ChAc) and a nuclear localization signal (NLS).
- Demonstration of Accum™'s adaptability to ADCs and antigens for various cancer types.
- Validation of endosome escape and nuclear routing as critical for intracellular accumulation and target cell selectivity.
Main Results:
- Accum™ was biochemically characterized and shown to be adaptable for conjugation with ADCs and antigens.
- Endosome escape and nuclear routing mediated by Accum™ were confirmed as essential for enhanced intracellular accumulation and target cell selectivity.
- Coupling Accum™ to ADCs significantly increased tumor cytotoxicity, while coupling to tumor antigens enhanced anti-cancer immunogenicity.
Conclusions:
- Accum™ effectively facilitates endosome escape and nuclear targeting, enhancing the intracellular accumulation and functionalization of coupled biologics.
- The unique mechanism of action of Accum™ leads to improved therapeutic outcomes, including enhanced tumor cytotoxicity and durable anti-cancer immunogenicity.
- Accum™ shows significant promise for clinical translation in onco-immunotherapy due to its adaptability, mechanism, and therapeutic potency.
Keywords:
Accumcancercholic acidcompromised activityendosome entrapmentfunctionalizing biotechnologyimmunogenicityintracellular accumulationnuclear localization signalprimerMore Related Videos
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