T cell receptor-transgenic primary T cells as a tool for discovery of leukaemia-associated antigens

Ivanov, Roman; Hol, Samantha; Aarts, Tineke; Hagenbeek, Anton; Ebeling, Saskia B.

doi:10.1111/j.1365-2249.2005.02967.x

Cited by 6 publications

(3 citation statements)

References 15 publications

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“…Since then, many TCRs that target peptide/MHCs derived from tumor- or virus-associated/specific antigens have been cloned and expressed in normal T cells, to redirect T cell specificity, including TCRs targeting the following: an epitope derived from melanoma-associated antigen 3 (MAGE-A3) [33]; melanoma antigen recognized by T cells 1 (MART-1) [34–36]; human immunodeficiency virus (HIV) Gag and Pol antigens [37, 38]; hepatitis C virus (HCV) non-structure protein 3 (NS3) [39]; Epstein-Barr virus (EBV) [40]; latent membrane protein 2 (LMP2) [41]; mouse double-minute 2 (MDM2) [42]; New York esophageal squamous cell carcinoma-1 (NY-ESO-1) [43]; melanoma-associated antigen 1 (MAGE-A1) [44]; glycoprotein 100 (gp100) [45, 46]; tumor protein p53 (P53) [47]; human papillomavirus (HPV) 16E7 [48]; minor histocompatibility antigens (mHag) [49]; minor histocompatibility antigen HA-1 (HA-1) [50]; ubiquitously transcribed tetratricopeptide repeat gene on the Y chromosome (UTY) [51]; ribosomal protein S4, Y-linked (RPS4Y) [52]; tyrosinase [53]; the MHC class-II-restricted dead-box RNA helicase Y (DBY) [54]; cytotoxic T cell (CTL)-recognized antigen on melanoma (CAMEL) [55]; Wilms’ tumor 1 (WT1) [56, 57]; a renal cell carcinoma (RCC) tumor antigen [58]; mouse mastocytoma P815 [59]; and carcinoembryonic antigen (CEA) [60]. Pre-clinical studies of these TCRs have demonstrated that the TCR-transduced T cells can recognize tumor cells expressing the specific antigen with the same MHC alleles.…”

Section: Pre-clinical Studies Of Tcr-t Therapymentioning

confidence: 99%

Targeting cancers through TCR-peptide/MHC interactions

et al. 2019

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Adoptive T cell therapy has achieved dramatic success in a clinic, and the Food and Drug Administration approved two chimeric antigen receptor-engineered T cell (CAR-T) therapies that target hematological cancers in 2018. A significant issue faced by CART therapies is the lack of tumor-specific biomarkers on the surfaces of solid tumor cells, which hampers the application of CART therapies to solid tumors. Intracellular tumor-related antigens can be presented as peptides in the major histocompatibility complex (MHC) on the cell surface, which interact with the T cell receptors (TCR) on antigen-specific T cells to stimulate an anti-tumor response. Multiple immunotherapy strategies have been developed to eradicate tumor cells through targeting the TCR-peptide/MHC interactions. Here, we summarize the current status of TCR-based immunotherapy strategies, with particular focus on the TCR structure, activated signaling pathways, the effects and toxicity associated with TCR-based therapies in clinical trials, preclinical studies examining immune-mobilizing monoclonal TCRs against cancer (ImmTACs), and TCR-fusion molecules. We propose several TCR-based therapeutic strategies to achieve optimal clinical responses without the induction of autoimmune diseases.

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Section: Pre-clinical Studies Of Tcr-t Therapymentioning

confidence: 99%

Targeting cancers through TCR-peptide/MHC interactions

et al. 2019

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“…A more feasible approach to generate sufficient number of functional T cells for therapeutic transfer has been the production of TCR-transgenic T cells restricted to a particular tumor epitope [92,93]. This approach uses viral transfer of the genes encoding the TCR α and β chains of identified tumor-specific clones into primary T cells.…”

Section: Production Of Bulk T Cells As a Tool For Discovery Of Taamentioning

confidence: 99%

Strategies for the Identification of T Cell–Recognized Tumor Antigens in Hematological Malignancies for Improved Graft-versus-Tumor Responses after Allogeneic Blood and Marrow Transplantation

Zilberberg

Feinman

Korngold

2015

Biology of Blood and Marrow Transplantation

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Allogeneic blood and marrow transplantation (allo-BMT) is an effective immunotherapeutic treatment that can provide partial or complete remission for patients with hematological malignancies. Mature donor T cells in the donor inoculum play a central role in mediating graft-versus-tumor (GVT) responses by destroying residual tumor cells that persist after conditioning regimens. Alloreactivity towards minor histocompatibility antigens (miHA), which are varied tissue-related self-peptides presented in the context of major histocompatibility complex (MHC) molecules on recipient cells, some of which may be shared on tumor cells, is a dominant factor for the development of GVT. Potentially, GVT can also be directed to tumor-associated antigens or tumor-specific antigens that are more specific to the tumor cells themselves. The full exploitation of allo-BMT, however, is greatly limited by the development of graft-versus-host disease (GVHD), which is mediated by the donor T cell response against the miHA expressed in the recipient’s cells of the intestine, skin, and liver. Because of the significance of GVT and GVHD responses in determining the clinical outcome of patients, miHA and tumor antigens have been intensively studied, and one active immunotherapeutic approach to separate these two responses has been cancer vaccination after allo-BMT. The combination of these two strategies has an advantage over vaccination of the patient without allo-BMT because his or her immune system has already been exposed and rendered unresponsive to the tumor antigens. The conditioning for allo-BMT eliminates the patient’s existing immune system, including regulatory elements, and provides a more permissive environment for the newly developing donor immune compartment to selectively target the malignant cells. Utilizing recent technological advances, the identities of many human miHA and tumor antigenic peptides have been defined and are currently being evaluated in clinical and basic immunological studies for their ability to produce effective T cell responses. The first step towards this goal is the identification of targetable tumor antigens. In this review, we will highlight some of the technologies currently used to identify tumor antigens and anti-tumor T cell clones in hematological malignancies.

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“…Heemskerk and colleagues were the first to describe the transfer of a mHag-specific TCR (HA-2, Heemskerk et al, 2003). Other specificities that have been transferred are HA-1, UTY, and RPS4Y (Ivanov et al, 2005;Mommaas et al, 2005;Ivanov et al, 2006), and the MHC class II restricted DBY (van der Veken et al., 2005). It remains to be shown whether these TCR modified T cells with single antigen specificities are as effective in clinical settings as the allogeneic T cells used for donor lymphocyte transfusions.…”

Section: Tcr Gene-modified T Cellsmentioning

confidence: 96%