VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens

Autores
Carri, Ibel; Schwab, Erika; Trivino, Juan Carlos; Von Euw, Erika María; Nielsen, Morten; Mordoh, José; Barrios, María Marcela
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
VACCIMEL is a therapeutic cancer vaccine composed of four irradiated allogeneic human melanoma cell lines rationally selected to cover a wide range of melanoma tumor-associated antigens (TAA). We previously demonstrated that vaccination in the adjuvant setting prolonged the distant-metastasis-free survival of cutaneous melanoma patients and that T cells reactive to TAA and the patient’s private neoantigens increased during treatment. However, immune responses directed to vaccine antigens that may arise from VACCIMEL’s somatic mutations and human polymorphisms remain unexplored. To study these immunogens, we performed whole-exome sequencing of paired tumor and germinal samples from four vaccinated patients and the vaccine cells. VACCIMEL variants were called by comparing the vaccine and the patient’s exomes, and non-synonymous coding variants were used to predict T cell epitopes. Candidates were ranked based on their mRNA expression in VACCIMEL, predicted peptide-HLA (pHLA) presentation, and pHLA stability. Then, the immune responses to prioritized epitope candidates were tested using IFNγ ELISpot assays on vaccinated patients’ PBMC samples. The comparison of the vaccine with the patients’ germinal exomes revealed on average 9481 coding non-synonymous variants, suggesting that VACCIMEL offers a high number of potential antigens. Between 0,05 and 0,2% of these variants were also found in the tumors of three vaccinated patients; however, one patient with a high tumor mutational burden (TMB) shared 19,5% somatic variants. The assessment of T cell responses showed that vaccinated patients mounted highly diverse responses against VACCIMEL peptides. Notably, effector T cells targeting the patient’s tumor antigens, comprising neoantigens and TAA, were found in higher frequencies than T cells targeting VACCIMEL-exclusive antigens. On the other hand, we observed that the immunogenic epitopes are not conserved across patients, despite sharing HLA and that immune responses fluctuate over time. Finally, a positive correlation between VACCIMEL antigen expression and the intensity of the T cell responses was found. Our results demonstrate that the immune system simultaneously responds to a high number of antigens, either vaccinal or private, proving that immune responses against epitopes not expressed in the patient’s tumors were not detrimental to the immune recognition of neoantigens and TAA.
Fil: Carri, Ibel. Fundación P/la Invest.y Prevención del Cancer. Centro de Investigaciones Oncologicas; Argentina. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Schwab, Erika. Fundación P/la Invest.y Prevención del Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Trivino, Juan Carlos. No especifíca;
Fil: Von Euw, Erika María. University of California at Los Angeles; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Mordoh, José. Fundación P/la Invest.y Prevención del Cancer. Centro de Investigaciones Oncologicas; Argentina
Fil: Barrios, María Marcela. Fundación P/la Invest.y Prevención del Cancer. Centro de Investigaciones Oncologicas; Argentina
Materia
cancer immunotherapy
whole cancer cell vaccine
allogeneic vaccine
VACCIMEL
neoantigen
melanoma
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/266195

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network_name_str CONICET Digital (CONICET)
spelling VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigensCarri, IbelSchwab, ErikaTrivino, Juan CarlosVon Euw, Erika MaríaNielsen, MortenMordoh, JoséBarrios, María Marcelacancer immunotherapywhole cancer cell vaccineallogeneic vaccineVACCIMELneoantigenmelanomahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1VACCIMEL is a therapeutic cancer vaccine composed of four irradiated allogeneic human melanoma cell lines rationally selected to cover a wide range of melanoma tumor-associated antigens (TAA). We previously demonstrated that vaccination in the adjuvant setting prolonged the distant-metastasis-free survival of cutaneous melanoma patients and that T cells reactive to TAA and the patient’s private neoantigens increased during treatment. However, immune responses directed to vaccine antigens that may arise from VACCIMEL’s somatic mutations and human polymorphisms remain unexplored. To study these immunogens, we performed whole-exome sequencing of paired tumor and germinal samples from four vaccinated patients and the vaccine cells. VACCIMEL variants were called by comparing the vaccine and the patient’s exomes, and non-synonymous coding variants were used to predict T cell epitopes. Candidates were ranked based on their mRNA expression in VACCIMEL, predicted peptide-HLA (pHLA) presentation, and pHLA stability. Then, the immune responses to prioritized epitope candidates were tested using IFNγ ELISpot assays on vaccinated patients’ PBMC samples. The comparison of the vaccine with the patients’ germinal exomes revealed on average 9481 coding non-synonymous variants, suggesting that VACCIMEL offers a high number of potential antigens. Between 0,05 and 0,2% of these variants were also found in the tumors of three vaccinated patients; however, one patient with a high tumor mutational burden (TMB) shared 19,5% somatic variants. The assessment of T cell responses showed that vaccinated patients mounted highly diverse responses against VACCIMEL peptides. Notably, effector T cells targeting the patient’s tumor antigens, comprising neoantigens and TAA, were found in higher frequencies than T cells targeting VACCIMEL-exclusive antigens. On the other hand, we observed that the immunogenic epitopes are not conserved across patients, despite sharing HLA and that immune responses fluctuate over time. Finally, a positive correlation between VACCIMEL antigen expression and the intensity of the T cell responses was found. Our results demonstrate that the immune system simultaneously responds to a high number of antigens, either vaccinal or private, proving that immune responses against epitopes not expressed in the patient’s tumors were not detrimental to the immune recognition of neoantigens and TAA.Fil: Carri, Ibel. Fundación P/la Invest.y Prevención del Cancer. Centro de Investigaciones Oncologicas; Argentina. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Schwab, Erika. Fundación P/la Invest.y Prevención del Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Trivino, Juan Carlos. No especifíca;Fil: Von Euw, Erika María. University of California at Los Angeles; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Mordoh, José. Fundación P/la Invest.y Prevención del Cancer. Centro de Investigaciones Oncologicas; ArgentinaFil: Barrios, María Marcela. Fundación P/la Invest.y Prevención del Cancer. Centro de Investigaciones Oncologicas; ArgentinaFrontiers Media2025-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/266195Carri, Ibel; Schwab, Erika; Trivino, Juan Carlos; Von Euw, Erika María; Nielsen, Morten; et al.; VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens; Frontiers Media; Frontiers in Immunology; 15; 1-2025; 1-151664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2024.1496204/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2024.1496204info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:20:14Zoai:ri.conicet.gov.ar:11336/266195instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:20:14.458CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens
title VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens
spellingShingle VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens
Carri, Ibel
cancer immunotherapy
whole cancer cell vaccine
allogeneic vaccine
VACCIMEL
neoantigen
melanoma
title_short VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens
title_full VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens
title_fullStr VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens
title_full_unstemmed VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens
title_sort VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens
dc.creator.none.fl_str_mv Carri, Ibel
Schwab, Erika
Trivino, Juan Carlos
Von Euw, Erika María
Nielsen, Morten
Mordoh, José
Barrios, María Marcela
author Carri, Ibel
author_facet Carri, Ibel
Schwab, Erika
Trivino, Juan Carlos
Von Euw, Erika María
Nielsen, Morten
Mordoh, José
Barrios, María Marcela
author_role author
author2 Schwab, Erika
Trivino, Juan Carlos
Von Euw, Erika María
Nielsen, Morten
Mordoh, José
Barrios, María Marcela
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv cancer immunotherapy
whole cancer cell vaccine
allogeneic vaccine
VACCIMEL
neoantigen
melanoma
topic cancer immunotherapy
whole cancer cell vaccine
allogeneic vaccine
VACCIMEL
neoantigen
melanoma
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv VACCIMEL is a therapeutic cancer vaccine composed of four irradiated allogeneic human melanoma cell lines rationally selected to cover a wide range of melanoma tumor-associated antigens (TAA). We previously demonstrated that vaccination in the adjuvant setting prolonged the distant-metastasis-free survival of cutaneous melanoma patients and that T cells reactive to TAA and the patient’s private neoantigens increased during treatment. However, immune responses directed to vaccine antigens that may arise from VACCIMEL’s somatic mutations and human polymorphisms remain unexplored. To study these immunogens, we performed whole-exome sequencing of paired tumor and germinal samples from four vaccinated patients and the vaccine cells. VACCIMEL variants were called by comparing the vaccine and the patient’s exomes, and non-synonymous coding variants were used to predict T cell epitopes. Candidates were ranked based on their mRNA expression in VACCIMEL, predicted peptide-HLA (pHLA) presentation, and pHLA stability. Then, the immune responses to prioritized epitope candidates were tested using IFNγ ELISpot assays on vaccinated patients’ PBMC samples. The comparison of the vaccine with the patients’ germinal exomes revealed on average 9481 coding non-synonymous variants, suggesting that VACCIMEL offers a high number of potential antigens. Between 0,05 and 0,2% of these variants were also found in the tumors of three vaccinated patients; however, one patient with a high tumor mutational burden (TMB) shared 19,5% somatic variants. The assessment of T cell responses showed that vaccinated patients mounted highly diverse responses against VACCIMEL peptides. Notably, effector T cells targeting the patient’s tumor antigens, comprising neoantigens and TAA, were found in higher frequencies than T cells targeting VACCIMEL-exclusive antigens. On the other hand, we observed that the immunogenic epitopes are not conserved across patients, despite sharing HLA and that immune responses fluctuate over time. Finally, a positive correlation between VACCIMEL antigen expression and the intensity of the T cell responses was found. Our results demonstrate that the immune system simultaneously responds to a high number of antigens, either vaccinal or private, proving that immune responses against epitopes not expressed in the patient’s tumors were not detrimental to the immune recognition of neoantigens and TAA.
Fil: Carri, Ibel. Fundación P/la Invest.y Prevención del Cancer. Centro de Investigaciones Oncologicas; Argentina. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Schwab, Erika. Fundación P/la Invest.y Prevención del Cancer. Centro de Investigaciones Oncologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Trivino, Juan Carlos. No especifíca;
Fil: Von Euw, Erika María. University of California at Los Angeles; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Mordoh, José. Fundación P/la Invest.y Prevención del Cancer. Centro de Investigaciones Oncologicas; Argentina
Fil: Barrios, María Marcela. Fundación P/la Invest.y Prevención del Cancer. Centro de Investigaciones Oncologicas; Argentina
description VACCIMEL is a therapeutic cancer vaccine composed of four irradiated allogeneic human melanoma cell lines rationally selected to cover a wide range of melanoma tumor-associated antigens (TAA). We previously demonstrated that vaccination in the adjuvant setting prolonged the distant-metastasis-free survival of cutaneous melanoma patients and that T cells reactive to TAA and the patient’s private neoantigens increased during treatment. However, immune responses directed to vaccine antigens that may arise from VACCIMEL’s somatic mutations and human polymorphisms remain unexplored. To study these immunogens, we performed whole-exome sequencing of paired tumor and germinal samples from four vaccinated patients and the vaccine cells. VACCIMEL variants were called by comparing the vaccine and the patient’s exomes, and non-synonymous coding variants were used to predict T cell epitopes. Candidates were ranked based on their mRNA expression in VACCIMEL, predicted peptide-HLA (pHLA) presentation, and pHLA stability. Then, the immune responses to prioritized epitope candidates were tested using IFNγ ELISpot assays on vaccinated patients’ PBMC samples. The comparison of the vaccine with the patients’ germinal exomes revealed on average 9481 coding non-synonymous variants, suggesting that VACCIMEL offers a high number of potential antigens. Between 0,05 and 0,2% of these variants were also found in the tumors of three vaccinated patients; however, one patient with a high tumor mutational burden (TMB) shared 19,5% somatic variants. The assessment of T cell responses showed that vaccinated patients mounted highly diverse responses against VACCIMEL peptides. Notably, effector T cells targeting the patient’s tumor antigens, comprising neoantigens and TAA, were found in higher frequencies than T cells targeting VACCIMEL-exclusive antigens. On the other hand, we observed that the immunogenic epitopes are not conserved across patients, despite sharing HLA and that immune responses fluctuate over time. Finally, a positive correlation between VACCIMEL antigen expression and the intensity of the T cell responses was found. Our results demonstrate that the immune system simultaneously responds to a high number of antigens, either vaccinal or private, proving that immune responses against epitopes not expressed in the patient’s tumors were not detrimental to the immune recognition of neoantigens and TAA.
publishDate 2025
dc.date.none.fl_str_mv 2025-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/266195
Carri, Ibel; Schwab, Erika; Trivino, Juan Carlos; Von Euw, Erika María; Nielsen, Morten; et al.; VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens; Frontiers Media; Frontiers in Immunology; 15; 1-2025; 1-15
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/266195
identifier_str_mv Carri, Ibel; Schwab, Erika; Trivino, Juan Carlos; Von Euw, Erika María; Nielsen, Morten; et al.; VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens; Frontiers Media; Frontiers in Immunology; 15; 1-2025; 1-15
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2024.1496204/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2024.1496204
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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