Immunotherapeutic Strategies as Potential Treatment Options for Cutaneous Leishmaniasis

Abstract

Cutaneous leishmaniasis (CL), caused by protozoan parasites of the Leishmania genus, is prevalent in tropical and subtropical regions, with important morbidity, particularly in low- to middle-income countries. Current systemic treatments, including pentavalent antimonials and miltefosine, are associated with significant toxicity, reduced efficacy, and are frequently ineffective in cases of severe or chronic CL. Immunotherapies leverage the immune system to combat microbial infection and offer a promising adjunct or alternative approach to the current standard of care for CL. However, the heterogeneous clinical presentation of CL, which is dependent on parasite species and host immunity, may require informed clinical intervention with immunotherapies. This review explores the clinical and immunological characteristics of CL, emphasising the current landscape of immunotherapies in in vivo models and clinical studies. Such immune-based interventions aim to modulate immune responses against Leishmania, with additive therapeutic effects enabling the efficacy of lower drug doses and decreasing the associated toxicity. Understanding the mechanisms that underlie immunotherapy for CL provides critical insights into developing safer and more effective treatments for this neglected tropical disease. Identifying suitable therapeutic candidates and establishing their safety and efficacy are essential steps in this process. However, the feasibility and utility of these treatments in resource-limited settings must also be considered, taking into account factors such as cost of production, temperature stability, and overall patient access.

Keywords: TLR agonism; cutaneous leishmaniasis; immunotherapy; therapeutic vaccination.

Figure 1

Landscape of potential immunotherapeutic approaches to treat CL. Depending on the form of CL, immunotherapies aim to promote parasitic clearance and/or disease resolution by enhancing the Th1 response, decreasing the Th2 response, or dampening exacerbated Th1/Th17 inflammatory responses. BCG, Bacillus Calmette–Guerin; CD4⁺, CD4⁺ T cells; DC, dendritic cells; N, neutrophils; Mφ, macrophages; Th1, T helper 1 cytokines; Th2, T helper 2 cytokines; Th17, T helper 17 cytokines; TLR, toll-like receptor; Treg, regulatory T cell cytokines.