Cytotoxic T cell response against the chimeric ETV6-AML1 protein in childhood acute lymphoblastic leukemia.

Yotnda, Patricia; Garcı́a, Fernando; Grandchamp, Bernard; Duval, Michel; Lemonnier, F; Vilmer, E; Langlade‐Demoyen, Pierre

doi:10.1172/jci3126

Cited by 104 publications

(21 citation statements)

References 22 publications

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“…[43]. Similar results have been observed for the t(12;21), which occurs in approximately 25% of ALL patients [44]. Recent studies have also shown evidence for binding of breakpoint peptides derived from t(X;18) in synovial cell sarcoma, as well as t (11;22) in desmoplastic small round cell tumor, to common HLA alleles (Helman LJ, Manuscript in preparation), suggesting that these peptides could also potentially serve as immunogens in these tumors.…”

Section: Figure 1 Presentation Of Peptides Derived From Intracellulasupporting

confidence: 85%

Targeting pediatric malignancies for T cell-mediated immune responses

Mackall

Helman

2000

Curr Oncol Rep

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Successful immune targeting of malignancies hinges upon the ability to activate specific T-cell populations to recognize and attack tumor but spare normal vital tissues. Investigators in the field of tumor immunology are currently utilizing at least three distinct approaches toward this goal. In the first approach, molecular targets of cytolytic T cells which spontaneously develop in tumor-bearing patients have been identified and are subsequently used as immunogens in immunotherapy trials. Whereas this approach originally focused upon the identification of tumor antigens in the immune-responsive tumors malignant melanoma and renal cell carcinoma, it surprisingly led to the identification of a variety of molecules that are now known to be expressed in other common pediatric and adult tumors. In the second approach, tumor-specific molecules (eg, mutant p53 and chromosomal translocations) that have been identified in individual tumors during the study of neoplastic transformation are used as immunogens. Because chromosomal translocations are common in pediatric tumors, such targets may be of particular interest in pediatric oncology. In the third approach, immunization with whole tumor cell components is undertaken with the assumption that the most immunogenic molecules within the tumor will dominate the immune response induced. The benefits and limitations for each approach, particularly as it pertains to the development of immunotherapy for pediatric tumors, are discussed in this article.

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Section: Figure 1 Presentation Of Peptides Derived From Intracellulasupporting

confidence: 85%

Targeting pediatric malignancies for T cell-mediated immune responses

Mackall

Helman

2000

Curr Oncol Rep

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“…CD8 T cells against a mutated p53, K-ras or N-ras peptide could be isolated after in vitro stimulation of T cells originating from healthy donor or patients injected with peptide pulsed APC or autologous irradiated tumor cells [66][67][68]. Peptides derived from frameshift mutations [69,70] or chromosomal translocations [71,72] were also identified.…”

Section: Tumor Antigens Recognized By Cytolytic T Lymphocytesmentioning

confidence: 99%

Insights into the processing of MHC class I ligands gained from the study of human tumor epitopes

Vigneron

Eynde

2011

Cell. Mol. Life Sci.

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The molecular definition of tumor antigens recognized by cytolytic T lymphocytes (CTL) started in the late 1980s, at a time when the MHC class I antigen processing field was in its infancy. Born together, these two fields of science evolved together and provided each other with critical insights. Over the years, stimulated by the potential interest of tumor antigens for cancer immunotherapy, scientists have identified and characterized numerous antigens recognized by CTL on human tumors. These studies have provided a wealth of information relevant to the mode of production of antigenic peptides presented by MHC class I molecules. A number of tumor antigenic peptides were found to result from unusual mechanisms occurring at the level of transcription, translation or processing. Although many of these mechanisms occur in the cell at very low level, they are relevant to the immune system as they determine the killing of tumor cells by CTL, which are sensitive to low levels of peptide/MHC complexes. Moreover, these unusual mechanisms were found to occur not only in tumor cells but also in normal cells. Thereby, the study of tumor antigens has illuminated many aspects of MHC class I processing. We review here those insights into the MHC I antigen processing pathway that result from the characterization of human tumor antigens recognized by CTL.

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“…Einige Leukämien besitzen aufgrund einer charakteristischen genetischen Translokation leukämiespezifische Antigene, z. B. das BCR-ABL-Fusionsprotein als Folge der t(9;22)-Translokation (Philadelphia-Chromosom) oder ETV6-RUNX1 bei akuten lymphoblastischen Leukämien mit t(12;21)-Translokation [29]. Trotz ihrer einzigartigen Spezifität erwiesen sich diese Antigene nicht als geeignete Zielstrukturen, weil sie nur eine geringe Immunogenität besitzen und darüber hinaus eine breite Anwendung bei der Mehrzahl der Leukämien nicht möglich ist.…”

Section: Therapeutisch Nutzbare Tumorspezifische Antigeneunclassified

T-Zell-Therapien bei Leukämie

Rettinger

2010

Monatsschr Kinderheilkd

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Die Mehrzahl der Leukämien des Kindesalters kann heute mit einer Polychemotherapie erfolgreich behandelt werden. In Hochrisikosituationen kann eine Therapieintensivierung mit nachfolgender allogener hämatopoetischer Stammzelltransplantation (HSZT) erheblich zur Erhaltung der Remission beitragen [5, 22]. Rezidive nach Transplantation verlaufen in aller Regel fatal. Für die Betroffenen werden dringend neue Behandlungskonzepte benötigt. Durch die Möglichkeit der Quantifizierung der minimalen Resterkrankung mit Hilfe molekularer Methoden können Patienten mit hohem Rezidivrisiko heute frühzeitig identifiziert werden [2], sodass sich ein therapeutisches Fenster für innovative Therapieverfahren ergibt. Ein Behandlungsansatz besteht dann in der gezielten Verabreichung antileukämischer zytotoxischer T-Zellen. Immuntherapie mit zytotoxischen T-ZellenZytotoxische T-Zellen spielen bei der Immunantwort gegen Virusinfektionen und Tumoren eine wesentliche Rolle. Sie erkennen Zellen über antigenspezifische Rezeptoren und sind in der Lage, ihre Zielzellen mit hoher Effektivität zu lysieren. Die Attraktivität von T-Zell-Therapien ist in erster Linie auf die einzigartige Spezifität des zellulären Immunsystems und die Gedächtnisfunktion spezifischer T-Zellen zurückzuführen. So kommt es bei erneutem Antigenkontakt zu einer zügigen und wirkungsvollen Immunreaktion. Im Rahmen einer Reaktivierung können T-Zellen im Körper verbliebene maligne Zellen immunologisch kontrollieren und eine langfristige Remission erhalten.

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Cytotoxic T cell response against the chimeric ETV6-AML1 protein in childhood acute lymphoblastic leukemia.

Cited by 104 publications

References 22 publications

Targeting pediatric malignancies for T cell-mediated immune responses

Targeting pediatric malignancies for T cell-mediated immune responses

Insights into the processing of MHC class I ligands gained from the study of human tumor epitopes

T-Zell-Therapien bei Leukämie

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