CD155 Expression in Acute Myeloid Leukemia

NCT ID: NCT06369662

Last Updated: 2024-10-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

93 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-07-01

Study Completion Date

2024-05-31

Brief Summary

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Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy. It is the most common form of acute leukemia among adults. In the United States, an estimated 19,940 people will be diagnosed with AML in 2020.

CD155 expression was associated with an unfavorable prognosis in solid tumors such as colon cancer, breast cancer, lung adenocarcinoma, pancreatic cancer, melanoma, and glioblastoma, as it correlated with tumor migration, development of metastases, tissue and lymph node invasion, relapse, and poorer survival.

Detailed Description

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Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy. It is the most common form of acute leukemia among adults. In the United States, an estimated 19,940 people will be diagnosed with AML in 2020.

T-cell exhaustion is a state of decline in T-cell proliferation and function (secretion of cytokines and cytotoxicity). It is defined by the expression of immune checkpoints including programmed cell death protein-1 (PD1), cytotoxic T-lymphocyte-associated protein-4 (CTLA4), T-cell immunoglobulin and mucin-domain containing-3 (TIM3), lymphocyte-activation gene-3 (LAG3), T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT), and CD160. This phenomenon was observed in many cancer cells to escape from antitumor immune responses.

The poliovirus receptor (PVR), also known as CD155, is an immunoglobulin -like adhesion molecule, with an important regulatory role in T-cell and natural killer (NK) cell functions, cell migration and proliferation. It is a major ligand that is expressed on epithelial and myeloid cells of the tumor. PVR is able to bind CD226, DNAX accessory molecule-1 (DNAM-1), T-cell-Activated Increased Late Expression Protein (TACTILE), and TIGIT. Binding to DNAM-1 induces the release of pro-inflammatory cytokines and cytotoxicity of T-cells and NK cells (T-cell activation), while binding to TIGIT induces a rather anti-inflammatory, non-proliferative, and noncytotoxic profile (T-cell exhaustion).

CD155 expression was associated with an unfavorable prognosis in solid tumors such as colon cancer, breast cancer, lung adenocarcinoma, pancreatic cancer, melanoma, and glioblastoma, as it correlated with tumor migration, development of metastases, tissue and lymph node invasion, relapse, and poorer survival.

Stamm et al., demonstrated that high CD155 (PVR) expression correlated with poor outcome in AML. Stamm et al., also showed that antibody blockade of PVR on AML cell lines or primary AML cells or TIGIT blockade on immune cells increased the anti-leukemic effects mediated by purified CD3+ cells in vitro. Zhang et al., assessed the prognostic significance and immune-associated mechanism of CD155 and identified that CD155 was commonly upregulated in most human cancers including AML, and high expression of CD155 was closely correlated with unfavorable clinical outcomes.

Our aim is to study the prognostic and predictive values of CD155 expression in AML patients in our locality.

Conditions

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Neoplasms Hematologic Neoplasms Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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AML Patients

Adult patients (from 18 - 60 years) diagnosed as AML

Flow cytometric immunophenotyping

Intervention Type DIAGNOSTIC_TEST

CD155 expression by flow cytometric immunophenotyping

Complete blood count

Intervention Type DIAGNOSTIC_TEST

Complete blood count with peripheral blood smear examination

Bone marrow aspiration

Intervention Type DIAGNOSTIC_TEST

Bone marrow aspiration at both diagnosis and follow up of patients

Cytogenetic testing

Intervention Type DIAGNOSTIC_TEST

Karyotyping or AML fluorescence in situ hybridization (FISH) panel for diagnosis and risk stratification of AML patients

FLT3-ITD using High resolution melting curve (HRM) analysis

Intervention Type DIAGNOSTIC_TEST

Detection of FLT3-ITD mutation in AML patinets

Interventions

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Flow cytometric immunophenotyping

CD155 expression by flow cytometric immunophenotyping

Intervention Type DIAGNOSTIC_TEST

Complete blood count

Complete blood count with peripheral blood smear examination

Intervention Type DIAGNOSTIC_TEST

Bone marrow aspiration

Bone marrow aspiration at both diagnosis and follow up of patients

Intervention Type DIAGNOSTIC_TEST

Cytogenetic testing

Karyotyping or AML fluorescence in situ hybridization (FISH) panel for diagnosis and risk stratification of AML patients

Intervention Type DIAGNOSTIC_TEST

FLT3-ITD using High resolution melting curve (HRM) analysis

Detection of FLT3-ITD mutation in AML patinets

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Patients with newly diagnosed AML.
* Age group: patients more than 18 years old and less than 60 years.
* Patients receiving induction chemotherapy 3\&7 at South Egypt Cancer Institute.

Exclusion Criteria

* Patients less than 18 years old and over 60 years.
* Patients with concurrent malignancy.
* Secondary AML.
* Acute Promyelocytic leukemia (AML-M3).
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assiut University

OTHER

Sponsor Role lead

Responsible Party

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Nehal Adel Rayan Mohamed

Assistant Lecturer

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Nehal Rayan, M.D.

Role: PRINCIPAL_INVESTIGATOR

Assistant Lecturer

Locations

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South Egypt Cancer Institute, Assiut University

Asyut, , Egypt

Site Status

Countries

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Egypt

References

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Dougall WC, Kurtulus S, Smyth MJ, Anderson AC. TIGIT and CD96: new checkpoint receptor targets for cancer immunotherapy. Immunol Rev. 2017 Mar;276(1):112-120. doi: 10.1111/imr.12518.

Reference Type BACKGROUND
PMID: 28258695 (View on PubMed)

Gao J, Zheng Q, Xin N, Wang W, Zhao C. CD155, an onco-immunologic molecule in human tumors. Cancer Sci. 2017 Oct;108(10):1934-1938. doi: 10.1111/cas.13324. Epub 2017 Aug 18.

Reference Type BACKGROUND
PMID: 28730595 (View on PubMed)

Gorvel L, Olive D. Targeting the "PVR-TIGIT axis" with immune checkpoint therapies. F1000Res. 2020 May 13;9:F1000 Faculty Rev-354. doi: 10.12688/f1000research.22877.1. eCollection 2020.

Reference Type BACKGROUND
PMID: 32489646 (View on PubMed)

Li XY, Das I, Lepletier A, Addala V, Bald T, Stannard K, Barkauskas D, Liu J, Aguilera AR, Takeda K, Braun M, Nakamura K, Jacquelin S, Lane SW, Teng MW, Dougall WC, Smyth MJ. CD155 loss enhances tumor suppression via combined host and tumor-intrinsic mechanisms. J Clin Invest. 2018 Jun 1;128(6):2613-2625. doi: 10.1172/JCI98769. Epub 2018 May 14.

Reference Type BACKGROUND
PMID: 29757192 (View on PubMed)

Liu L, Chang YJ, Xu LP, Zhang XH, Wang Y, Liu KY, Huang XJ. T cell exhaustion characterized by compromised MHC class I and II restricted cytotoxic activity associates with acute B lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation. Clin Immunol. 2018 May;190:32-40. doi: 10.1016/j.clim.2018.02.009. Epub 2018 Mar 15.

Reference Type BACKGROUND
PMID: 29477343 (View on PubMed)

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590. Epub 2020 Jan 8.

Reference Type BACKGROUND
PMID: 31912902 (View on PubMed)

Zhang H, Yang Z, Du G, Cao L, Tan B. CD155-Prognostic and Immunotherapeutic Implications Based on Multiple Analyses of Databases Across 33 Human Cancers. Technol Cancer Res Treat. 2021 Jan-Dec;20:1533033820980088. doi: 10.1177/1533033820980088.

Reference Type BACKGROUND
PMID: 33576304 (View on PubMed)

Bakhshaei P, Kazemi MH, Golara M, Abdolmaleki S, Khosravi-Eghbal R, Khoshnoodi J, Judaki MA, Salimi V, Douraghi M, Jeddi-Tehrani M, Shokri F. Investigation of the Cellular Immune Response to Recombinant Fragments of Filamentous Hemagglutinin and Pertactin of Bordetella pertussis in BALB/c Mice. J Interferon Cytokine Res. 2018 Apr;38(4):161-170. doi: 10.1089/jir.2017.0060.

Reference Type RESULT
PMID: 29638208 (View on PubMed)

Other Identifiers

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SECI-IRB-IORG0006563-545

Identifier Type: OTHER

Identifier Source: secondary_id

SECI-CD155

Identifier Type: -

Identifier Source: org_study_id

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