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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Cancer Immunity and Immunotherapy

This article is part of the Research TopicTranslational Research on Cancer Immunity and Immunotherapy: Preclinical and Clinical Investigations from Latin AmericaView all articles

UNRAVELLING THE COMPLEXITY OF THE INTERACTIONS AMONG VACCIMEL, BCG AND BLOOD MONOCYTES

Provisionally accepted
Erika  SchwabErika Schwab1,2Brenda  CarlesBrenda Carles2ALICIA  INES BRAVOALICIA INES BRAVO2,3María  Victoria EcheniqueMaría Victoria Echenique2Agustina  De FrancAgustina De Franc4Mariano  Guillermo BonannoMariano Guillermo Bonanno3María  Marcela BarrioMaría Marcela Barrio2José  MordohJosé Mordoh2*
  • 1Universidad de Buenos Aires Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina
  • 2Centro de Investigaciones Oncológicas, Fundación Cáncer, Buenos Aires, Capital federal, Argentina
  • 3Hospital Interzonal General de Agudos Eva Peron, Buenos Aires, Argentina
  • 4LANAIS-MIE, Instituto de Biología Celular y Neurociencia Prof. E. De Robertis, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

The final, formatted version of the article will be published soon.

VACCIMEL is an immunotherapeutic adjuvant treatment for high-risk cutaneous melanoma. It consists of 13 intradermal injections of four irradiated melanoma cell lines co-adjuvated with BCG and GM-CSF. VACCIMEL prolongs distant metastases-free survival and it induces T lymphocytes reactive against melanoma differentiation antigens, cancer testis antigens, and neoantigens. In this paper, we have studied in vitro the interaction among VACCIMEL, BCG, and blood-derived monocytes, a fundamental component of innate immunity. We have demonstrated that monocytes may phagocytose, separately and jointly, BCG and VACCIMEL. We have demonstrated for the first time by transmission electron microscopy, detailed features of irradiated melanoma cells phagocytosis and its timeline. We have equally demonstrated that monocytes may process and cross-present tumor antigens to CD8+ T cells and that BCG interferes with that process in a multiplicity of infection (MOI) - dependent manner. BCG induces high production of IL-10 by monocytes which is several-fold reduced by phagocytosis of tumor antigens. Although cross-presentation is still inhibited in the presence of a high BCG MOI (0.4), it rebounds by reducing tenfold the BCG MOI from 0.4 to 0.04. This suggests that an adequate balance between tumor antigens and BCG phagocytosis is needed to retain the stimulatory properties of activated monocytes and trigger immunogenicity of tumor antigens.

Keywords: BCG, cutaneous melanoma, Immunotherapy, innate immune cells, Monocytes, Phagocytosis

Received: 23 Oct 2025; Accepted: 11 Feb 2026.

Copyright: © 2026 Schwab, Carles, BRAVO, Echenique, De Franc, Bonanno, Barrio and Mordoh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: José Mordoh

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