Immunophenotypic Markers
Wojciech Gorczyca in Atlas of Differential Diagnosis in Neoplastic Hematopathology, 2014
CD7 is a membrane-bound glycoprotein that is expressed very early in T-cell development. CD7 is a pan-T-cell antigen expressed by peripheral (mature) T-cell lymphoproliferations (e.g., PTCL, T-PLL, ATLL, MF, SS, T-LGL leukemia, NK cell leukemia/lymphoma), and T-ALL. CD7 is very often aberrantly expressed (either negative or dim) in peripheral T-cell disorders. In precursor T-cell neoplasms, CD7 is most often positive and shows a bright expression when analyzed by flow cytometry (only ~2% cases are CD7−). Other hematopoietic tumors that may express CD7 include BPDCN, MPAL, and AML. APL and B-cell lymphoproliferations are typically CD7−.
T Cells:Regulation and Cellular Immunity
Constantin A. Bona, Francisco A. Bonilla in Textbook of Immunology, 2019
Several cell-surface molecules serve as markers of T cell differentiation. The marker expressed earliest in T cell development is CD7. This early stage is not yet committed to the T cell lineage, and may enter erythroid, myeloid, or megakaryocytoid pathways. The role of CD7 in T cell differentiation is unknown. Some CD7+ cells also express CD34. Both CD7+/CD34+ and CD7+/CD34− cells may become either T cells or other cell types. The function of CD34 is also unknown.
Integrins, Integrin Regulators, and the Extracellular Matrix
Bruce S. Bochner in Adhesion Molecules in Allergic Disease, 2020
The complexity of inside-out signaling is illustrated by the identification of multiple activation stimuli that can up-regulate integrin functional activity. These activation signals can be grouped as pharmacologic agents or receptor-mediated signals. Treatment of T cells with either the phorbol ester PMA or the Ca2+ ionophore A23187 has been shown to up-regulate integrin-mediated T-cell adhesion (28,41,43,44). This suggests that both protein kinase C (PKC) activation and changes in intracellular Ca2+ are involved in the intracellular signaling events that upregulate integrin activity. More significantly, mAb-mediated cross-linking of a litany of cell surface receptors can induce an inside-out signal. Such receptors are designated “integrin regulators” in this review. Leukocytes express a wide array of integrin regulators on the cell surface. Using T cells as an example, ligation of a number of cell surface receptors can result in up-regulation of β1 and β2 integrin functional activity. T-cell integrin regulators include the CD3/TCR complex, as well as the accessory molecules CD2, CD28, and CD7 (41–43). CD2, CD7, and CD28 are all IgSF members. The CD2 antigen is a 45–55 kD protein that was initially identified as an important signaling molecule on human T cells and NK cells (45,46). Subsequently, CD2 was shown to mediate T-cell adhesion by binding to its counter-receptor, LFA-3 (47). The CD28 antigen is a 44 kD molecule that has been extensively studied because of its importance in delivering a signal to T cells that is believed to be critical to the prevention of T-cell tolerance upon encounter with antigen (48). At least two distinct CD28 counter-receptors, B7–1 and B7–2, have been identified and there has been extensive analysis of CD28-mediated signaling as it relates to T-cell proliferation and cytokine production (48). CD7 is a 40 kD antigen that is expressed on T cells and NK cells. The function of CD7 is unknown at present. All three of these integrin regulators facilitate CD3-mediated T cell proliferation, suggesting that inside-out signaling mediated by these molecules is particularly important in enhancing T cell responses to foreign antigen.
Immunotoxins and nanobody-based immunotoxins: review and update
Published in Journal of Drug Targeting, 2021
Mohammad Reza Khirehgesh, Jafar Sharifi, Fatemeh Safari, Bahman Akbari
The cluster of differentiation 7 (CD7) is one of the cell surface glycoproteins that overexpresses in leukaemia and T-cell lymphoma. VHH6 is an anti-CD7 Nb that use to design two monovalent and bivalent PG001 (VHH-PE38) and PG002 (VHH-VHH-PE38) recombinant ITs, respectively. After the expression of PG001 and PG002, the binding activities of them were assessed on a high expression CD7 cell line (Jurkat) by flow cytometry assays. Also, Wst 8 assay by CD7 positive cell lines showed that PG002 was powerful than PG001 in proliferation inhibition [158]. For the immunogenicity reduction and cytotoxic activity improvement of PG002, three new formats developed include dVHH6-PE-LR, dhuVHH6-PE38, and dhuVHH6-PE-LR. After the expression of these recombinant ITs, the flow cytometry assay confirmed their high affinity to the positive CD7 cell lines (CEM and Jurkat). In vivo assessment of the humanised ITs (dhuVHH6-PE38 and dhuVHH6-PE-LR) in NOD-Prkdcem26I12rgem26Nju (NCG) mice xenotransplanted with CEM cells showed that dhuVHH6-PE38 had better antitumour activity and extends the survival of NCG [159].
T cells expressing CD26-specific chimeric antigen receptors exhibit extensive self-antigen-driven fratricide
Published in Immunopharmacology and Immunotoxicology, 2019
Shu Zhou, Xiaoying Zhu, Na Shen, Qing Li, Na Wang, Yong You, Zhaodong Zhong, Fanjun Cheng, Ping Zou, Xiaojian Zhu
However, after repeated trials and experiments, we found that the activated T cells transduced with anti-CD26-4-1BB-CAR induced fratricide partly due to the shared CD26 expressing on activated T cells. The phenomenon was proved not only by the indirect evidence that the CD26 CAR T cells had poor viability and failed to expand, but also that the CD26 CAR T cells showed direct cytotoxicity against CFSE-labeled autologous T cells. The fratricide in T cells expressing anti-CD5-CD28-CAR is transient and does not limit their expansion, which is attributed to the rapid downregulation of CD5 from the cell surface of CAR T cells, reflecting the property of CD5 internalization upon binding to the specific antibody [13]. Unlike CD5 CAR T cells, the internalization of CD7 from the T cells surface following CAR expression is incomplete and results in extensive fratricide of CD7 CAR T cells [14]. Remarkably, an additional knockout of the CD7 gene by CRISPR/Cas9 renders CD7 CAR T cells resistant to fratricide, permitting robust expansion and function to target T-cell malignance [14]. Therefore, we have tried to investigate that whether the fratricide of CD26 CAR T cells can be reversed by disrupting CD26 expressing of activated T cells. Regrettably, the effect of knockout of the CD26 by CD26-siRNA was limited and transient, and the expressing of CD26 was up-regulated following the activation of T cells (Supplemental Figure 2). The method of CRISPR/Cas9 may help to conquer this problem.
T-cell acute lymphoblastic leukemia: promising experimental drugs in clinical development
Published in Expert Opinion on Investigational Drugs, 2023
First studies using CD7CAR T cells showed an incomplete downregulation of CD7 on transduced CAR T cells leading to fratricide [131]. Abrogating CD7 expression was then proposed by various specific techniques, such as blockade of CD7 protein trafficking [132], and CRISPR/Cas9 gene editing [133]. Consequently, a robust anti-tumor activity was observed in both preclinical and clinical studies against CD7+ T-ALL. Another risk with CD7CAR T cells is T-cell depletion and immunodeficiency. Activation of an inducible suicide gene was proposed to avoid such side effects [134]. Fratricide-resistant anti-CD7 CAR T cells have also been developed from healthy donors [133]. These allogeneic CAR T cells have the advantage to be immediately available but also to eliminate the risk of graft-versus-host disease (GvHD). Several studies using CD7CAR T cells, involving overall more than 40 T-ALL patients, have already been published [135–139]. ORR and CR ranged from 63% to 100%. CRS was observed in all cases.
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