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Cancers
Volume 13
Issue 22
10.3390/cancers13225801
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Article

A Personalized Neoantigen Vaccine in Combination with Platinum-Based Chemotherapy Induces a T-Cell Response Coinciding with a Complete Response in Endometrial Carcinoma

by
Alexandre Harari
1,2,*,†,
Apostolos Sarivalasis
3,†,
Kaat de Jonge
1,
Anne-Christine Thierry
1,
Florian Huber
1,2,
Caroline Boudousquie
1,
Laetitia Rossier
1,
Angela Orcurto
3,
Martina Imbimbo
3,
Petra Baumgaertner
1,
Michal Bassani-Sternberg
1,2 and
Lana E. Kandalaft
1,2,3,*
1
Center of Experimental Therapeutics, Department of Oncology, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland
2
Ludwig Institute for Cancer Research, University of Lausanne (UNIL), 1005 Lausanne, Switzerland
3
Department of Oncology, Lausanne University Hospital (CHUV), 1011, Lausanne, Switzerland
*
Authors to whom correspondence should be addressed.
†
These authors have equally contributed.
Academic Editors: Pierandrea De Iac, Anna Myriam Perrone and David Wong
Cancers 2021, 13(22), 5801; https://doi.org/10.3390/cancers13225801
Received: 28 September 2021 / Revised: 10 November 2021 / Accepted: 16 November 2021 / Published: 18 November 2021
(This article belongs to the Special Issue Endometrial Cancer: Old Questions and New Perspectives)
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Simple Summary

We investigated the feasibility and immunogenicity of an autologous Dendritic Cell (DC) vaccine pulsed with peptide neoantigens in combination with a standard of care regimen. The vaccine program took place in a serous endometrial mismatch repair (MMR) deficiency setting. We demonstrate for the first time the feasibility of producing a peptide DC vaccine in endometrial carcinoma. The safety and immunogenicity of this personalized vaccine was demonstrated by the detection of polyfunctional and durable T-cell responses.

Abstract

Endometrial cancer (EC) is a common gynecological malignancy and the fourth most common malignancy in European and North American women. Amongst EC, the advanced serous, p53-mutated, and pMMR subtypes have the highest risk of relapse despite optimal standard of care therapy. At present, there is no standard of care maintenance treatment to prevent relapse among these high-risk patients. Vaccines are a form of immunotherapy that can potentially increase the immunogenicity of pMMR, serous, and p53-mutated tumors to render them responsive to check point inhibitor-based immunotherapy. We demonstrate, for the first time, the feasibility of generating a personalized dendritic cell vaccine pulsed with peptide neoantigens in a patient with pMMR, p53-mutated, and serous endometrial adenocarcinoma (SEC). The personalized vaccine was administered in combination with systemic chemotherapy to treat an inoperable metastatic recurrence. This treatment association demonstrated the safety and immunogenicity of the personalized dendritic cell vaccine. Interestingly, a complete oncological response was obtained with respect to both radiological assessment and the tumor marker CA-125. View Full-Text
Keywords: endometrial cancer; cancer vaccines; immunotherapy; neoantigens endometrial cancer; cancer vaccines; immunotherapy; neoantigens
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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MDPI and ACS Style

Harari, A.; Sarivalasis, A.; de Jonge, K.; Thierry, A.-C.; Huber, F.; Boudousquie, C.; Rossier, L.; Orcurto, A.; Imbimbo, M.; Baumgaertner, P.; Bassani-Sternberg, M.; Kandalaft, L.E. A Personalized Neoantigen Vaccine in Combination with Platinum-Based Chemotherapy Induces a T-Cell Response Coinciding with a Complete Response in Endometrial Carcinoma. Cancers 2021, 13, 5801. https://doi.org/10.3390/cancers13225801

AMA Style

Harari A, Sarivalasis A, de Jonge K, Thierry A-C, Huber F, Boudousquie C, Rossier L, Orcurto A, Imbimbo M, Baumgaertner P, Bassani-Sternberg M, Kandalaft LE. A Personalized Neoantigen Vaccine in Combination with Platinum-Based Chemotherapy Induces a T-Cell Response Coinciding with a Complete Response in Endometrial Carcinoma. Cancers. 2021; 13(22):5801. https://doi.org/10.3390/cancers13225801

Chicago/Turabian Style

Harari, Alexandre, Apostolos Sarivalasis, Kaat de Jonge, Anne-Christine Thierry, Florian Huber, Caroline Boudousquie, Laetitia Rossier, Angela Orcurto, Martina Imbimbo, Petra Baumgaertner, Michal Bassani-Sternberg, and Lana E. Kandalaft. 2021. "A Personalized Neoantigen Vaccine in Combination with Platinum-Based Chemotherapy Induces a T-Cell Response Coinciding with a Complete Response in Endometrial Carcinoma" Cancers 13, no. 22: 5801. https://doi.org/10.3390/cancers13225801

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