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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/266195
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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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13.22299 |