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3 results on '"Merino Díaz M"'

1. Design and in vitro / in vivo evaluation of a targeted immunotherapy platform for the treatment of melanoma

Author

Merino-Díaz, M. (María), Garrido, M.J. (María Jesús), and Zalba, S. (Sara)

Subjects
Anticuerpos, Farmacología, Farmacia::Farmacia y farmacología [Materias Investigacion], Preparación de fármacos
Abstract

The proposal of this work has been the combination of immunotherapy and chemotherapy, applying the advantages of nanotechnology. To achieve the present aim, several steps represented in the different chapters have been addressed. First, a detailed review about the state of the art of immunoliposomes (ILs), as well as a summary about the main key points that have to be controlled to develop adequate ILs, are reported in Chapter 1. Chapter 2 is focused on the development of different ILs coupled with a specific monoclonal antibody (mAb), the anti-PD-L1 and its Fab fragment, using different PEG percentages in the liposome composition and coupling methods, to be, all of them, later assayed in in vitro / in vivo studies. Here, factors such as ligand density and orientation have been optimized, making an important effort to achieve a formulation able to deal with adequate characteristics to reach the tumor area and produce efficient cellular uptake/internalization and immune activity. Finally, in Chapter 3, the formulation selected in the previous work has been combined with Doxorobucin (Dox) as a proof of concept, to evaluate its in vitro / in vivo activity. This immune-nanoplatform encapsulating Dox and targeted against PD-L1 showed a dual mechanism characterized by an immune stimulation and a cytotoxic activity, both contributing to reduce and eliminate cancer cells.

Published
2019

2. Dual activity of PD-L1 targeted Doxorubicin immunoliposomes promoted an enhanced efficacy of the antitumor immune response in melanoma murine model

Author

Merino-Díaz, M. (María)

Subjects
Liposome, PD-L1, Doxorubicin, Chemo-immunotherapy, Immunotherapy, Immunogenic cell death, Melanoma, Immunocheckpoint
Abstract

Background: The immunomodulation of the antitumor response driven by immunocheckpoint inhibitors (ICIs) such as PD-L1 (Programmed Death Ligand-1) monoclonal antibody (alpha-PD-L1) have shown relevant clinical outcomes in a subset of patients. This fact has led to the search for rational combinations with other therapeutic agents such as Doxorubicin (Dox), which cytotoxicity involves an immune activation that may enhance ICI response. Therefore, this study aims to evaluate the combination of chemotherapy and ICI by developing Dox Immunoliposomes functionalized with monovalent-variable fragments (Fab') of alpha-PD-L1. Results: Immunoliposomes were assayed in vitro and in vivo in a B16 OVA melanoma murine cell line over-expressing PD-L1. Here, immune system activation in tumor, spleen and lymph nodes, together with the antitumor efficacy were evaluated. Results showed that immunoliposomes bound specifically to PD-L1(+) cells, yielding higher cell interaction and Dox internalization, and decreasing up to 30-fold the IC50, compared to conventional liposomes. This mechanism supported a higher in vivo response. Indeed, immunoliposomes promoted full tumor regression in 20% of mice and increased in 1 month the survival rate. This formulation was the only treatment able to induce significant (p < 0.01) increase of activated tumor specific cytotoxic T lymphocytes at the tumor site. Conclusion: PD-L1 targeted liposomes encapsulating Dox have proved to be a rational combination able to enhance the modulation of the immune system by blocking PD-L1 and selectively internalizing Dox, thus successfully providing a dual activity offered by both, chemo and immune therapeutic strategies.

Published
2021

3. Effectiveness of Modified Vaccinia Ankara-Bavaria Nordic Vaccination in a Population at High Risk of Mpox: A Spanish Cohort Study.

Author

Fontán-Vela M, Hernando V, Olmedo C, Coma E, Martínez M, Moreno-Perez D, Lorusso N, Vázquez Torres M, Barbas Del Buey JF, Roig-Sena J, Pastor E, Galmés Truyols A, Artigues Serra F, Sancho Martínez RM, Latasa Zamalloa P, Pérez Martínez O, Vázquez Estepa A, García Rojas AJ, Barreno Estévez AI, Sánchez-Migallón Naranjo A, Pérez Martín JJ, Peces Jiménez P, Morales Romero R, Castilla J, García Cenoz M, Huerta Huerta M, Boone ALD, Macías Ortiz MJ, Álvarez Río V, Rodríguez Recio MJ, Merino Díaz M, Berradre Sáenz B, Villegas-Moreno MT, Limia A, Diaz A, and Monge S

Subjects
Humans, Adolescent, Adult, Cohort Studies, Retrospective Studies, Vaccinia virus, Vaccination, Monkeypox virus, Vaccinia prevention & control, Mpox (monkeypox), Vaccines, HIV Infections epidemiology, HIV Infections prevention & control
Abstract

Background: With more than 7500 cases reported since April 2022, Spain has experienced the highest incidence of mpox in Europe. From 12 July onward, the modified vaccinia Ankara-Bavaria Nordic (MVA-BN) smallpox vaccine was offered as pre-exposure prophylaxis for those receiving pre-exposure prophylaxis for human immunodeficiency virus (HIV-PrEP). Our aim was to assess the effectiveness of 1 dose of MVA-BN vaccine as pre-exposure prophylaxis against mpox virus (MPXV) infection in persons on HIV-PrEP., Methods: National retrospective cohort study between 12 July and 12 December 2022. Individuals aged ≥18 years receiving HIV-PrEP as of 12 July with no previous MPXV infection or vaccination were eligible. Each day, we matched individuals receiving a first dose of vaccine and unvaccinated controls of the same age and region. We used a Kaplan-Meier estimator, calculated risk ratios (RR) and vaccine effectiveness (VE = [1 - RR]x100)., Results: We included 5660 matched pairs, with a median follow-up of 62 days (interquartile range, 24-97). Mpox cumulative incidence was 5.6 per 1000 (25 cases) in unvaccinated and 3.5 per 1000 (18 cases) in vaccinated. No effect was found during days 0-6 post-vaccination (VE, -38.3; 95% confidence interval [CI], -332.7 to 46.4), but VE was 65% at ≥7 days (95% CI, 22.9 to 88.0) and 79% at ≥14 days (95% CI, 33.3 to 100.0) post-vaccination., Conclusions: One dose of MVA-BN vaccine offered protection against mpox in most-at-risk population shortly after the vaccination. Further studies need to assess the VE of a second dose and the duration of protection over time., Competing Interests: Potential conflicts of interest. A. G. T. reports financial support for expert testimony from Moderna and GSK and for attending meetings and/or travel from Pfizer and MSD. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Published
2024
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