Drug delivery targets and strategies to address mast cell diseases

ABSTRACT

Introduction

Current and developing mast cell therapeutics are reliant on small molecule drugs and biologics, but few are truly selective for mast cells. Most have cellular and disease-specific limitations that require innovation to overcome longstanding challenges to selectively targeting and modulating mast cell behavior. This review is designed to serve as a frame of reference for new approaches that utilize nanotechnology or combine different drugs to increase mast cell selectivity and therapeutic efficacy.

Areas covered

Mast cell diseases include allergy and related conditions as well as malignancies. Here, we discuss the targets of existing and developing therapies used to treat these disease pathologies, classifying them into cell surface, intracellular, and extracellular categories. For each target discussed, we discuss drugs that are either the current standard of care, under development, or have indications for potential use. Finally, we discuss how novel technologies and tools can be used to take existing therapeutics to a new level of selectivity and potency against mast cells.

Expert opinion

There are many broadly and very few selectively targeted therapeutics for mast cells in allergy and malignant disease. Combining existing targeting strategies with technology like nanoparticles will provide novel platforms to treat mast cell disease more selectively.

KEYWORDS:

• Mast cells
• allergy
• cancer
• mastocytosis
• nanoparticles
• cell targeting

Article highlights

• There is a lack of selective and potent medications available to directly regulate mast cell activity in allergy or malignant disease.

• Existing approved mast cell therapies are dominated by small molecule drugs, the majority of which have varying unintended side-effects due to a lack of mast cell selectivity.

• Powerful multi-omics approaches have aided in identifying novel mast cell targets.

• Modern methods of generating biologics, drug conjugates, and nanotherapies have opened the door to more selective mast cell therapeutics.

• Some antibody and receptor-specific strategies pose significant risk of uncontrolled rupture or activation of mast cells, potentially leading to dangerous anaphylactic responses.

• There are multiple mast cell targets which have potential to be employed for both allergic and malignant mast cell diseases, highlighting a likely benefit of collaboration and crossover between these research specialties.

This box summarizes key points contained in the article.

Declaration of interest

BS Bochner receives remuneration for serving on the scientific advisory board of Allakos, Inc. and owns stock in Allakos. He receives consulting fees from Third Harmonic Bio, Lupagen, Sanofi, and Acelyrin. He is a co-inventor on existing Siglec-8–related patents and thus may be entitled to a share of royalties received by Johns Hopkins University during development and potential sales of such products. BS Bochner is also a co-founder of Allakos, Inc. which makes him subject to certain restrictions under university policy. The terms of this arrangement are being managed by Johns Hopkins University and Northwestern University in accordance with their conflict-of-interest policies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper was funded by the National Institutes of Health (R21AI159586).