Evaluation of experimental immunotherapeutic formulations in the hybrid murine model of Graft-versus-Host Reaction

Authors

  • Li Hong Ying Universidad de Ciencias Médicas de La Habana, Instituto de Ciencias Básicas y Preclínicas “Victoria de Girón”. La Habana. Jiangxi Institute of Biological Products. Ji’An City,
  • Beatriz Tamargo Santos Escuela Latinoamericana de Medicina. La Habana. Jiangxi Institute of Biological Products. Ji’An City,
  • Juan F. Infante Bourzac Instituto Finlay de Vacunas. La Habana.
  • Reinaldo Oliva Hernández Instituto Finlay de Vacunas. La Habana.
  • Mildrey Fariñas Medina Instituto Finlay de Vacunas. La Habana.
  • Dasha Fuentes Morales Centro para Producción de Animales de Laboratorio (CENPALAB). Mayabeque.
  • V.Gustavo Sierra Gozález Grupo de las Industrias Biotecnológicas y Farmacéuticas de Cuba (BioCubaFarma). La Habana. Jiangxi Institute of Biological Products. Ji’An City.

Keywords:

Immunomodulators, Cochleate, Immunotherapy, Graft-Versus-Host Disease (GVHD), Murine model, Hematopoietic Stem Cell Transplants (HSCT), cytokines.

Abstract

Introduction: Graft-versus-host disease is the most frequent complication of Hematopoietic Stem Cell Transplants and all transplants containing allogeneic immunocompetent cells; 100% of patients suffer from this complication and about 30% die for this particular cause. A high proportion of cases are steroid-refractory; likewise, other modern immunosuppressive measures fail. In the fields of Immunotherapy and Vaccinology, there is also a worrying shortage of powerful, effective, safe and broad spectrum immunomodulators of biological origin. There is a hybrid murine model of great methodological utility for experimental studies.

Objective: To evaluate two novel formulations of biotechnological origin: an immunopotentiator formulation and an immunosuppressive one, which were developed as cochleates.

Material and Methods: The formulations assayed by Electron Microscopy and RT-PCR were characterized as nanoparticles and for their capacity to regulate lymphokine mRNA expression profile, respectively.  The immunomodulatory character was evaluated in vivo using Graft-versus-host disease in (CBAxC57BL) F1 hybrid mice.

Results: Starting from the proteoliposomes derived from Neisseria meningitides, two cochleate formulations were obtained, both with particle diameters below 100 nm. Formulation 1 showed a proinflammatory profile with potent capacity to increase IFNγ and TNFα, and potentiated the Spleen Index up to 2.05 in the GVDH model with p = 0.0002. Formulation 2 showed a suppressor/regulatory profile with potent capacity to increase IL-10 and TGFβ and suppress the production of TNFα. In the model used, this formulation suppressed the Spleen Index in a dose-dependent manner with high statistical significance. The known safety profile and absence of reactogenicity of both formulations was corroborated.

Conclusions: Both formulations have potential application in the fields of GVHD therapy and other pathologies as well as in Vaccinology.  The results obtained in the present work suggest the usefulness to continue with the pharmaceutical development and complete the preclinical studies of both formulations.

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Published

2020-02-16

How to Cite

1.
Hong Ying L, Tamargo Santos B, Infante Bourzac JF, Oliva Hernández R, Fariñas Medina M, Fuentes Morales D, et al. Evaluation of experimental immunotherapeutic formulations in the hybrid murine model of Graft-versus-Host Reaction. Rev haban cienc méd [Internet]. 2020 Feb. 16 [cited 2025 Jun. 21];19(1):10-29. Available from: https://revhabanera.sld.cu/index.php/rhab/article/view/3166

Issue

Vol. 19 No. 1: January-February 2020

Section

Biomedical Basic Sciences

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