Molecular Therapy: Methods & Clinical Development (Jun 2024)
Identifying MAGE-A4-positive tumors for TCR T cell therapies in HLA-A∗02-eligible patients
- Tianjiao Wang,
- Jean-Marc Navenot,
- Stavros Rafail,
- Cynthia Kurtis,
- Mark Carroll,
- Marian Van Kerckhoven,
- Sofie Van Rossom,
- Kelly Schats,
- Konstantinos Avraam,
- Robyn Broad,
- Karen Howe,
- Ashley Liddle,
- Amber Clayton,
- Ruoxi Wang,
- Laura Quinn,
- Joseph P. Sanderson,
- Cheryl McAlpine,
- Carly Carozza,
- Eric Pimpinella,
- Susan Hsu,
- Francine Brophy,
- Erica Elefant,
- Paige Bayer,
- Dennis Williams,
- Marcus O. Butler,
- Jeffrey M. Clarke,
- Justin F. Gainor,
- Ramaswamy Govindan,
- Victor Moreno,
- Melissa Johnson,
- Janet Tu,
- David S. Hong,
- George R. Blumenschein, Jr.
Affiliations
- Tianjiao Wang
- Clinical Biomarkers & Companion Diagnostics, Adaptimmune, Philadelphia, PA, USA; Corresponding author: Tianjiao Wang, Clinical Biomarkers & Companion Diagnostics, Adaptimmune, Philadelphia, PA, USA.
- Jean-Marc Navenot
- Clinical Biomarkers & Companion Diagnostics, Adaptimmune, Philadelphia, PA, USA; Corresponding author: Jean-Marc Navenot, Clinical Biomarkers & Companion Diagnostics, Adaptimmune, Philadelphia, PA, USA.
- Stavros Rafail
- Biomarker Discovery and Platform, Adaptimmune, Philadelphia, PA, USA
- Cynthia Kurtis
- Clinical Biomarkers & Companion Diagnostics, Adaptimmune, Philadelphia, PA, USA
- Mark Carroll
- Information Management Clinical Systems, Adaptimmune, Philadelphia, PA, USA
- Marian Van Kerckhoven
- Assay Development Histopathology, CellCarta, Antwerpen, Belgium
- Sofie Van Rossom
- Assay Development Histopathology, CellCarta, Antwerpen, Belgium
- Kelly Schats
- Assay Development Histopathology, CellCarta, Antwerpen, Belgium
- Konstantinos Avraam
- Histopathology & Image Quantification Unit, CellCarta, Antwerpen, Belgium
- Robyn Broad
- Translational Sciences, Adaptimmune, Abingdon, Oxfordshire, UK
- Karen Howe
- Target Validation, Adaptimmune, Abingdon, Oxfordshire, UK
- Ashley Liddle
- Translational Sciences, Adaptimmune, Abingdon, Oxfordshire, UK
- Amber Clayton
- Target Validation, Adaptimmune, Abingdon, Oxfordshire, UK
- Ruoxi Wang
- Information Management Clinical Systems, Adaptimmune, Philadelphia, PA, USA
- Laura Quinn
- Preclinical Research, Adaptimmune, Abingdon, Oxfordshire, UK
- Joseph P. Sanderson
- Preclinical Research, Adaptimmune, Abingdon, Oxfordshire, UK
- Cheryl McAlpine
- Translational Sciences, Adaptimmune, Abingdon, Oxfordshire, UK
- Carly Carozza
- Histocompatibility Laboratory Services, American Red Cross, Philadelphia, PA, USA
- Eric Pimpinella
- Histocompatibility Laboratory Services, American Red Cross, Philadelphia, PA, USA
- Susan Hsu
- Histocompatibility Laboratory Services, American Red Cross, Philadelphia, PA, USA
- Francine Brophy
- Clinical Science, Adaptimmune, Philadelphia, PA, USA
- Erica Elefant
- Clinical Science, Adaptimmune, Philadelphia, PA, USA
- Paige Bayer
- Clinical Science, Adaptimmune, Philadelphia, PA, USA
- Dennis Williams
- Late Stage Development, Adaptimmune, Philadelphia, PA, USA
- Marcus O. Butler
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Departments of Immunology and Medicine, University of Toronto, Toronto, ON, Canada
- Jeffrey M. Clarke
- Department of Medicine, Duke Cancer Institute, Durham, NC, USA
- Justin F. Gainor
- Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
- Ramaswamy Govindan
- Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
- Victor Moreno
- Oncology, START Madrid FJD, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
- Melissa Johnson
- Lung Cancer Research and Drug Development, Sarah Cannon Research Institute, Nashville, TN, USA
- Janet Tu
- Department of General Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- David S. Hong
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Corresponding author: David S. Hong, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- George R. Blumenschein, Jr.
- Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Corresponding author: George R. Blumenschein, Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Journal volume & issue
-
Vol. 32,
no. 2
p. 101265
Abstract
T cell receptor (TCR) T cell therapies target tumor antigens in a human leukocyte antigen (HLA)-restricted manner. Biomarker-defined therapies require validation of assays suitable for determination of patient eligibility. For clinical trials evaluating TCR T cell therapies targeting melanoma-associated antigen A4 (MAGE-A4), screening in studies NCT02636855 and NCT04044768 assesses patient eligibility based on: (1) high-resolution HLA typing and (2) tumor MAGE-A4 testing via an immunohistochemical assay in HLA-eligible patients. The HLA/MAGE-A4 assays validation, biomarker data, and their relationship to covariates (demographics, cancer type, histopathology, tissue location) are reported here. HLA-A∗02 eligibility was 44.8% (2,959/6,606) in patients from 43 sites across North America and Europe. While HLA-A∗02:01 was the most frequent HLA-A∗02 allele, others (A∗02:02, A∗02:03, A∗02:06) considerably increased HLA eligibility in Hispanic, Black, and Asian populations. Overall, MAGE-A4 prevalence based on clinical trial enrollment was 26% (447/1,750) across 10 solid tumor types, and was highest in synovial sarcoma (70%) and lowest in gastric cancer (9%). The covariates were generally not associated with MAGE-A4 expression, except for patient age in ovarian cancer and histology in non-small cell lung cancer. This report shows the eligibility rate from biomarker screening for TCR T cell therapies and provides epidemiological data for future clinical development of MAGE-A4-targeted therapies.
