BCG Immunotherapy in Equine Sarcoid Treatment: Mechanisms, Clinical Efficacy, and Challenges in Veterinary Oncology.
Abstract: Equine sarcoids are the most common dermatological neoplasm in horses worldwide, associated with bovine papillomavirus (BPV) infection and characterized by high recurrence rates after conventional therapies. Bacillus Calmette-Guérin (BCG) immunotherapy has historically been used for sarcoid treatment, yet its role in contemporary veterinary oncology remains debated. This narrative review critically examines the immunological mechanisms, clinical efficacy, and limitations of BCG in equine sarcoid therapy, while integrating insights from comparative oncology and One Health perspectives. A systematic search following PRISMA-based criteria identified 55 relevant studies published over the past four decades. Evidence indicates that BCG activates innate and adaptive immunity through TLR2/4 signaling, macrophage polarization, and enhanced CD8+ T-cell responses, leading to partial or complete sarcoid regression in select cases. However, therapeutic outcomes are highly variable due to heterogeneity in protocols (dose, strain, adjuvant use) and frequent adverse inflammatory reactions. Comparative analyses highlight that modern alternatives-such as cryotherapy, cisplatin-based protocols, and topical imiquimod-achieve higher efficacy and lower recurrence rates in many clinical settings. Although BCG is now rarely considered a first-line therapy, it remains relevant in resource-limited regions, such as the Amazon Biome, where cost-effectiveness and accessibility are critical. Future directions include randomized controlled trials, standardized protocols, and innovative approaches such as checkpoint inhibition, CRISPR-Cas9 targeting of viral oncogenes, and nanoparticle delivery systems. This review provides a balanced and data-driven synthesis of BCG immunotherapy, clarifying its historical contributions, current limitations, and translational opportunities for advancing equine and comparative oncology.
Publication Date: 2025-09-29 PubMed ID: 41157593PubMed Central: PMC12567874DOI: 10.3390/v17101322Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Review
Summary
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Overview
- This research article reviews the use of Bacillus Calmette-Guérin (BCG) immunotherapy for treating equine sarcoids, a common skin tumor in horses related to bovine papillomavirus infection.
- It evaluates the immunological mechanisms behind BCG, clinical effectiveness, challenges, and compares it with other modern treatments, while suggesting future research directions.
Background and Context
- Equine Sarcoids: The most frequent skin tumor in horses worldwide, often caused by bovine papillomavirus (BPV).
- Clinical Challenge: Sarcoids have high recurrence rates after conventional treatments such as surgery, cryotherapy, or chemical agents.
- BCG Immunotherapy: Historically used in veterinary oncology to stimulate the immune system in an attempt to regress or eliminate sarcoids.
- Relevance: Despite its historical use, BCG’s role today is debated due to variable efficacy and potential side effects.
Methodology
- The article is a narrative review based on a systematic literature search using PRISMA criteria.
- A total of 55 studies from the last 40 years were evaluated.
- Focus was on immunological mechanisms, clinical outcomes, therapy protocols, adverse effects, and comparative oncology perspectives.
Immunological Mechanisms of BCG in Sarcoid Treatment
- Immune Activation: BCG stimulates both innate and adaptive immune responses.
- Pattern Recognition: Through Toll-like receptors (TLR2 and TLR4), BCG activates macrophages and dendritic cells.
- Cell Polarization: Macrophage polarization enhances inflammatory and cytotoxic responses against tumor cells.
- Adaptive Responses: CD8+ T-cell activity is increased, promoting targeted killing of BPV-infected tumor cells.
- Result: These mechanisms contribute to partial or complete regression of sarcoids in some cases.
Clinical Efficacy and Variability
- BCG treatment results are highly variable across different cases.
- Variability is linked to:
- Differences in treatment protocols such as BCG dose, strain variation, and use of adjuvants.
- Inconsistent induction of immune responses between individual horses.
- Frequent adverse inflammatory reactions that can limit treatment tolerance.
- Although some horses show sarcoid regression, these outcomes are not reliably reproducible.
Comparative Oncology and Alternative Therapies
- Modern alternatives often demonstrate better outcomes and fewer side effects, including:
- Cryotherapy: Freezing tumors with liquid nitrogen.
- Cisplatin-based Protocols: Chemotherapeutic agents injected locally.
- Topical Imiquimod: An immune response modifier applied directly to sarcoids.
- These therapies frequently result in higher efficacy and lower sarcoid recurrence rates compared to BCG.
- The comparative analysis highlights the limited role of BCG as a first-line therapy in resource-rich clinical settings.
Contextual and Regional Considerations
- BCG remains relevant in resource-limited regions, such as the Amazon Biome, because:
- It is cost-effective compared to certain expensive alternatives.
- It is more accessible where advanced veterinary oncology resources are scarce.
- This underlines the importance of considering socio-economic and geographic factors in treatment choice.
Challenges and Limitations
- Protocol heterogeneity impedes consistent clinical application and assessment of efficacy.
- Adverse inflammatory effects are common and can complicate therapy.
- Lack of robust randomized controlled trials leaves many questions about optimal usage unanswered.
- BCG’s immunotherapeutic effect is not universally effective due to tumor and host immune system variability.
Future Directions and Innovations
- Call for randomized controlled trials to better define BCG’s place in therapy and optimize protocols.
- Development of standardized treatment protocols (dose, strain, administration method) is needed.
- Exploration of innovative therapies combining or replacing BCG, such as:
- Checkpoint inhibitors to enhance immune response against BPV-driven tumors.
- CRISPR-Cas9 gene-editing technology aimed at disrupting viral oncogenes in sarcoid cells.
- Nanoparticle-based delivery systems to improve targeting and reduce side effects.
- Integration of comparative oncology and One Health perspectives to translate findings between human and veterinary medicine.
Summary and Conclusion
- This review provides a balanced and evidence-based synthesis of BCG immunotherapy for equine sarcoids.
- It clarifies the immune mechanisms by which BCG works and highlights its historical significance in veterinary oncology.
- The article identifies the current limitations and variability in clinical outcomes leading to decreased use as a first choice treatment.
- Offers a forward-looking view emphasizing the potential for innovative immunotherapies to improve equine and comparative oncology treatment paradigms.
Cite This Article
APA
Monteiro MM, de Castro ELA, Pereira AJM, Thiesen R, Thiesen RMC, Salvarani FM.
(2025).
BCG Immunotherapy in Equine Sarcoid Treatment: Mechanisms, Clinical Efficacy, and Challenges in Veterinary Oncology.
Viruses, 17(10), 1322.
https://doi.org/10.3390/v17101322 Publication
Researcher Affiliations
- Instituto de Medicina Veterinária, Universidade Federal do Pará, Castanhal 68740-970, PA, Brazil.
- Instituto de Medicina Veterinária, Universidade Federal do Pará, Castanhal 68740-970, PA, Brazil.
- Instituto de Medicina Veterinária, Universidade Federal do Pará, Castanhal 68740-970, PA, Brazil.
- Instituto de Medicina Veterinária, Universidade Federal do Pará, Castanhal 68740-970, PA, Brazil.
- Instituto de Medicina Veterinária, Universidade Federal do Pará, Castanhal 68740-970, PA, Brazil.
- Instituto de Medicina Veterinária, Universidade Federal do Pará, Castanhal 68740-970, PA, Brazil.
MeSH Terms
- Animals
- Horses
- Horse Diseases / therapy
- Horse Diseases / immunology
- Immunotherapy / veterinary
- Immunotherapy / methods
- Skin Neoplasms / veterinary
- Skin Neoplasms / therapy
- Skin Neoplasms / immunology
- BCG Vaccine / therapeutic use
- BCG Vaccine / immunology
- Treatment Outcome
- Papillomavirus Infections / veterinary
- Sarcoidosis / veterinary
- Sarcoidosis / therapy
- Sarcoidosis / immunology
Conflict of Interest Statement
The authors declare no conflicts of interest.
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