A phase 1 trial of adoptive transfer of vaccine-primed autologous circulating T cells in ovarian cancer

Sara Bobisse^#^{1

2}, Valentina Bianchi^#^{1

2

3}, Janos L Tanyi^#⁴, Apostolos Sarivalasis², Edoardo Missiaglia^{5

6}, Rémy Pétremand^{1

2}, Fabrizio Benedetti^{1

2}, Drew A Torigian⁷, Raphael Genolet^{1

2}, David Barras^{1

2}, Alexandra Michel^{1

2}, Spyridon A Mastroyannis⁴, Emese Zsiros^{4

8}, Denarda Dangaj Laniti^{1

2}, Zoi Tsourti⁹, Brian J Stevenson^{1

2

6}, Christian Iseli^{6

10}, Bruce L Levine¹¹, Daniel E Speiser², David Gfeller^{1

2

6}, Michal Bassani-Sternberg^{1

2}, Daniel J Powell Jr¹¹, Carl H June¹¹, Urania Dafni⁹, Lana E Kandalaft^#^{1

2

3}, Alexandre Harari^#^{1

2}, George Coukos^#^{12

13}

Affiliations

¹ Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland.
² Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
³ Center for Experimental Therapeutics, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
⁴ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
⁵ Institute of Pathology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
⁶ SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
⁷ Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
⁸ Department of Gynecologic Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
⁹ Laboratory of Biostatistics, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece.
¹⁰ Bioinformatics Competence Center, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
¹¹ Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
¹² Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland. george.coukos@chuv.ch.
¹³ Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. george.coukos@chuv.ch.

^# Contributed equally.

PMID: 37735588
DOI: 10.1038/s43018-023-00623-x

Clinical Trial

A phase 1 trial of adoptive transfer of vaccine-primed autologous circulating T cells in ovarian cancer

Sara Bobisse et al. Nat Cancer. 2023 Oct.

. 2023 Oct;4(10):1410-1417.

doi: 10.1038/s43018-023-00623-x. Epub 2023 Sep 21.

Authors

Affiliations

¹ Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland.
² Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
³ Center for Experimental Therapeutics, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
⁴ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
⁵ Institute of Pathology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
⁶ SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
⁷ Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
⁸ Department of Gynecologic Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
⁹ Laboratory of Biostatistics, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece.
¹⁰ Bioinformatics Competence Center, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
¹¹ Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
¹² Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland. george.coukos@chuv.ch.
¹³ Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. george.coukos@chuv.ch.

^# Contributed equally.

PMID: 37735588
DOI: 10.1038/s43018-023-00623-x

Abstract

We have previously shown that vaccination with tumor-pulsed dendritic cells amplifies neoantigen recognition in ovarian cancer. Here, in a phase 1 clinical study ( NCT01312376 /UPCC26810) including 19 patients, we show that such responses are further reinvigorated by subsequent adoptive transfer of vaccine-primed, ex vivo-expanded autologous peripheral blood T cells. The treatment is safe, and epitope spreading with novel neopeptide reactivities was observed after cell infusion in patients who experienced clinical benefit, suggesting reinvigoration of tumor-sculpting immunity.

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References

1. Zhang, L. et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N. Engl. J. Med. 348, 203–213 (2003). - DOI - PubMed
1. Kandalaft, L. E., Dangaj Laniti, D. & Coukos, G. Immunobiology of high-grade serous ovarian cancer: lessons for clinical translation. Nat. Rev. Cancer 22, 640–656 (2022). - DOI - PubMed
1. Tanyi, J. L. et al. Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer. Sci. Transl. Med. 10, eaao5931 (2018). - DOI - PubMed
1. Hanker, L. C. et al. The impact of second to sixth line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapy. Ann. Oncol. 23, 2605–2612 (2012). - DOI - PubMed
1. Bobisse, S. et al. Sensitive and frequent identification of high avidity neo-epitope specific CD8⁺ T cells in immunotherapy-naive ovarian cancer. Nat. Commun. 9, 1092 (2018). - DOI - PubMed - PMC

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A phase 1 trial of adoptive transfer of vaccine-primed autologous circulating T cells in ovarian cancer

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A phase 1 trial of adoptive transfer of vaccine-primed autologous circulating T cells in ovarian cancer

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