A CD22-reactive TCR from the T-cell allorepertoire for the treatment of acute lymphoblastic leukemia by TCR gene transfer.
CD22 is currently evaluated as a target-antigen for the treatment of B-cell malignancies using chimeric antigen receptor (CAR)-engineered T-cells or monoclonal antibodies (mAbs). CAR- and mAbs-based immunotherapies have been successfully applied targeting other antigens, however, occurrence of refractory disease to these interventions urges the identification of additional strategies. Here, we identified a TCR recognizing the CD22-derived peptide RPFPPHIQL (CD22RPF) presented in human leukocyte antigen (HLA)-B*07:02. To overcome tolerance to self-antigens such as CD22, we exploited the immunogenicity of allogeneic HLA. CD22RPF-specific T-cell clone 9D4 was isolated from a healthy HLA-B*07:02neg individual, efficiently produced cytokines upon stimulation with primary acute lymphoblastic leukemia and healthy B-cells, but did not react towards healthy hematopoietic and nonhematopoietic cell subsets, including dendritic cells (DCs) and macrophages expressing low levels of CD22. Gene transfer of TCR-9D4 installed potent CD22-specificity onto recipient CD8+ T-cells that recognized and lysed primary B-cell leukemia. TCR-transduced T-cells spared healthy CD22neg hematopoietic cell subsets but weakly lysed CD22low-expressing DCs and macrophages. CD22-specific TCR-engineered T-cells could form an additional immunotherapeutic strategy with a complementary role to CAR- and antibody-based interventions in the treatment of B-cell malignancies. However, CD22 expression on non-B-cells may limit the attractiveness of CD22 as target-antigen in cellular immunotherapy.
Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Lorenz
L
Jahn
Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Renate S
RS
Hagedoorn
Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Dirk M
DM
van der Steen
Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.|Department of Hematopoiesis, Sanquin Research, 1006 AD Amsterdam, The Netherlands.
Pleun
P
Hombrink
Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Michel G D
MG
Kester
Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Marjolein P
MP
Schoonakker
Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Daniëlle
D
de Ridder
Center for Proteomics and Metabolomics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Peter A
PA
van Veelen
Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
J H Frederik
JH
Falkenburg
Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Mirjam H M
MH
Heemskerk
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes; D018014:Gene Transfer Techniques; D015235:HLA-B Antigens / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology*
C497867:CD22 protein, human; D000939:Epitopes; D015235:HLA-B Antigens; D011948:Receptors, Antigen, T-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2
CD22; TCR gene transfer; acute lymphoblastic leukemia; allogeneic HLA; immunotherapy
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