Sensitive identification of neoantigens and cognate TCRs in human solid tumors

Marion Arnaud; Johanna Chiffelle; Raphael Genolet; Blanca Navarro Rodrigo; Marta A S Perez; Florian Huber; Morgane Magnin; Tu Nguyen-Ngoc; Philippe Guillaume; Petra Baumgaertner; Chloe Chong; Brian J Stevenson; David Gfeller; Melita Irving; Daniel E Speiser; Julien Schmidt; Vincent Zoete; Lana E Kandalaft; Michal Bassani-Sternberg; Sara Bobisse; George Coukos; Alexandre Harari

doi:10.1038/s41587-021-01072-6

Sensitive identification of neoantigens and cognate TCRs in human solid tumors

Nat Biotechnol. 2022 May;40(5):656-660. doi: 10.1038/s41587-021-01072-6. Epub 2021 Nov 15.

Authors

Marion Arnaud^{1

2

3}, Johanna Chiffelle^{1

2

3}, Raphael Genolet^{1

2

3}, Blanca Navarro Rodrigo^{1

2

3}, Marta A S Perez^{1

4}, Florian Huber^{1

2

3}, Morgane Magnin^{1

2

3}, Tu Nguyen-Ngoc^{1

3}, Philippe Guillaume^{1

2

3}, Petra Baumgaertner^{1

2

3}, Chloe Chong^{1

2

3}, Brian J Stevenson^{1

4}, David Gfeller^{1

3

4}, Melita Irving^{1

3}, Daniel E Speiser^{1

3}, Julien Schmidt^{1

2

3}, Vincent Zoete^{1

3

4}, Lana E Kandalaft^{1

2

3}, Michal Bassani-Sternberg^{1

2

3}, Sara Bobisse^{1

2

3}, George Coukos^#^{5

6

7}, Alexandre Harari^#^{8

9

10}

Affiliations

¹ Ludwig Institute for Cancer Research, Lausanne Branch - University of Lausanne (UNIL), Lausanne, Switzerland.
² Centre des Thérapies Expérimentales (CTE), Department of Oncology - Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
³ Department of Oncology - University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland.
⁴ SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
⁵ Ludwig Institute for Cancer Research, Lausanne Branch - University of Lausanne (UNIL), Lausanne, Switzerland. george.coukos@chuv.ch.
⁶ Centre des Thérapies Expérimentales (CTE), Department of Oncology - Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. george.coukos@chuv.ch.
⁷ Department of Oncology - University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. george.coukos@chuv.ch.
⁸ Ludwig Institute for Cancer Research, Lausanne Branch - University of Lausanne (UNIL), Lausanne, Switzerland. alexandre.harari@chuv.ch.
⁹ Centre des Thérapies Expérimentales (CTE), Department of Oncology - Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. alexandre.harari@chuv.ch.
¹⁰ Department of Oncology - University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. alexandre.harari@chuv.ch.

^# Contributed equally.

Abstract

The identification of patient-specific tumor antigens is complicated by the low frequency of T cells specific for each tumor antigen. Here we describe NeoScreen, a method that enables the sensitive identification of rare tumor (neo)antigens and of cognate T cell receptors (TCRs) expressed by tumor-infiltrating lymphocytes. T cells transduced with tumor antigen-specific TCRs identified by NeoScreen mediate regression of established tumors in patient-derived xenograft mice.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, Neoplasm / genetics
CD8-Positive T-Lymphocytes
Humans
Lymphocytes, Tumor-Infiltrating
Mice
Neoplasms* / genetics
Neoplasms* / therapy
Receptors, Antigen, T-Cell* / genetics
T-Lymphocytes

Substances

Antigens, Neoplasm
Receptors, Antigen, T-Cell