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Artículo

Evaluation of T-Cell Responses Against Shared Melanoma Associated Antigens and Predicted Neoantigens in Cutaneous Melanoma Patients Treated With the CSF-470 Allogeneic Cell Vaccine Plus BCG and GM-CSF

Podaza, Enrique ArturoIcon ; Carri, IbelIcon ; Aris, MarianaIcon ; Von Euw, Erika MaríaIcon ; Bravo, Alicia Ines; Blanco, Paula; Ortiz Wilczyñski, Juan ManuelIcon ; Koile, Daniel IsaacIcon ; Yankilevich, PatricioIcon ; Nielsen, MortenIcon ; Mordoh, JoseIcon ; Barrio, Maria MarcelaIcon
Fecha de publicación: 06/2020
Editorial: Frontiers Media S.A.
Revista: Frontiers in Immunology
e-ISSN: 1664-3224
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Inmunología

Resumen

The CSF-470 vaccine consists of lethally-irradiated allogeneic cells derived from four cutaneous melanoma cell lines administered plus BCG and GM-CSF as adjuvants. In an adjuvant phase II study vs. IFN-α2b, the vaccine significantly prolonged the distant metastasis-free survival (DMFS) of stages IIB-IIC-III melanoma patients with evidence of the induction of immune responses against vaccine cells. Purpose: The aim of this study was to analyze the antigens against which the immune response was induced, as well as the T-helper profile and lytic ability of immune cells after CSF-470 treatment. Methods: HLA-restricted peptides from tumor-associated antigens (TAAs) were selected from TANTIGEN database for 13 evaluable vaccinated patients. In addition, for patient #006 (pt#006), tumor somatic variants were identified by NGS and candidate neoAgs were selected by predicted HLA binding affinity and similarity between wild type (wt) and mutant peptides. The patient‘s PBMC reactivity against selected peptides was detected by IFNγ-ELISPOT. T-helper transcriptional profile was determined by quantifying GATA-3, T-bet, and FOXP3 mRNA by RT-PCR, and intracellular cytokines were analyzed by flow cytometry. Autologous tumor cell lysis by PBMC was assessed in an in vitro calcein release assay. Results: Vaccinated patient‘s PBMC reactivity against selected TAAs derived peptides showed a progressive increase in the number of IFNγ-producing cells throughout the 2-yr vaccination protocol. ELISPOT response correlated with delayed type hypersensitivity (DTH) reaction to CSF-470 vaccine cells. Early upregulation of GATA-3 and Foxp3 mRNA, as well as an increase in CD4+IL4+cells, was associated with a low DMFS. Also, IFNγ response against 9/73 predicted neoAgs was evidenced in the case of pt#006; 7/9 emerged after vaccination. We verified in pt# 006 that post-vaccination PBMC boosted in vitro with the vaccine lysate were able to lyse autologous tumor cells. Conclusions: A progressive increase in the immune response against TAAs expressed in the vaccine and in the patient's tumor was induced by CSF-470 vaccination. In pt#006, we demonstrated immune recognition of patient's specific neoAgs, which emerged after vaccination. These results suggest that an initial response against shared TAAs could further stimulate an immune response against autologous tumor neoAgs.
Palabras clave: CSF-470 ALLOGENEIC CELL VACCINE , CUTANEOUS MELANOMA , MELANOMA IMMUNOTHERAPY , NEOANTIGENS , TUMOR ASSOCIATED ANTIGENS
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution 2.5 Unported (CC BY 2.5)
Identificadores
URI: http://hdl.handle.net/11336/139811
URL: https://www.frontiersin.org/article/10.3389/fimmu.2020.01147/full
DOI: https://doi.org/10.3389/fimmu.2020.01147
Colecciones
Articulos (IIBIO)
Articulos de INSTITUTO DE INVESTIGACIONES BIOTECNOLOGICAS
Articulos(IBIOBA - MPSP)
Articulos de INST. D/INV.EN BIOMED.DE BS AS-CONICET-INST. PARTNER SOCIEDAD MAX PLANCK
Articulos(IMEX)
Articulos de INST.DE MEDICINA EXPERIMENTAL
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Citación
Podaza, Enrique Arturo; Carri, Ibel; Aris, Mariana; Von Euw, Erika María; Bravo, Alicia Ines; et al.; Evaluation of T-Cell Responses Against Shared Melanoma Associated Antigens and Predicted Neoantigens in Cutaneous Melanoma Patients Treated With the CSF-470 Allogeneic Cell Vaccine Plus BCG and GM-CSF; Frontiers Media S.A.; Frontiers in Immunology; 11; 6-2020; 1-15
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