Applied Microbiology and Biotechnology

, Volume 103, Issue 19, pp 7903–7916 | Cite as

Mycobacterium bovis BCG in metastatic melanoma therapy

  • Martha Lucia Ruiz Benitez
  • Camila Bonnemann Bender
  • Thaís Larré Oliveira
  • Kyle M. Schachtschneider
  • Tiago Collares
  • Fabiana Kömmling SeixasEmail author


Melanoma is the most aggressive form of skin cancer, with a high mortality rate and with 96,480 new cases expected in 2019 in the USS. BRAFV600E, the most common driver mutation, is found in around 50% of melanomas, contributing to tumor growth, angiogenesis, and metastatic progression. Dacarbazine (DTIC), an alkylate agent, was the first chemotherapeutic agent approved by the US Food and Drug Administration (FDA) used as a standard treatment. Since then, immunotherapies have been approved for metastatic melanoma (MM) including ipilimumab and pembrolizumab checkpoint inhibitors that help decrease the risk of progression. Moreover, Mycobacterium bovis Bacillus Calmette–Guerin (BCG) serves as an adjuvant therapy that induces the recruitment of natural killer NK, CD4+, and CD8+ T cells and contributes to antitumor immunity. BCG can be administered in combination with chemotherapeutic and immunotherapeutic agents and can be genetically manipulated to produce recombinant BCG (rBCG) strains that express heterologous proteins or overexpress immunogenic proteins, increasing the immune response and improving patient survival. In this review, we highlight several studies utilizing rBCG immunotherapy for MM in combination with other therapeutic agents.


Bacillus Calmette–Guérin Recombinant BCG Immunotherapy Antitumor activity Skin cancer 


Funding information

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Laboratory of Cancer Biotechnology, Technology Development CenterFederal University of PelotasPelotasBrazil
  2. 2.Department of RadiologyUniversity of Illinois at ChicagoChicagoUSA
  3. 3.Department of Biochemistry & Molecular GeneticsUniversity of Illinois at ChicagoChicagoUSA
  4. 4.National Center for Supercomputing ApplicationsUniversity of Illinois at Urbana-ChampaignUrbanaUSA

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