"Don't Eat me" Signal in Hematological Malignancies: CD24 as New Target to Improve Anti-cancer Immunity.

NCT05888701 | Unknown

• 1 other identifier: CD24.DEM
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Mantle-cell Lymphoma (MCL) is a B-cell non-Hodgkin's lymphoma (NHL) with heterogeneous behavior,ranging from indolent phenotype to highly aggressive and drug resistant cases with dismal prognosis.Disease progression and drug resistance may be generated by Tumor Microenvironment (TME),owing that M2-like immunosuppressive tumor associated macrophages (TAM) are pathologically functional in providing survival signals to MCL cells-and TME is known to help mask tumoral cells from host immune system.Similarly, Chronic Lymphocytic Leukemia (CLL) is a B-cell malignancy characterized by increased circulating number of mature B lymphocytes that eventually reside into bone marrow and lymphoid tissues as well.Higher number of circulating abnormal B cells is secondary to a balance between increased proliferation and decreased apoptosis activities,sustained by signals also deriving from TME.As a matter of fact,TME harbors different cell compounds and monocyte-derived Nurse-like cells (NLCs) resemble the M2-like macrophage immunosuppressive profile and turned out to be an important component able to interact with CLL cells, providing improvement of proliferation and survival.Recently, cancer-expressed CD47 was found to be involved in tumor immune escape through interaction with Signal Regulatory Protein-α (SIRP-α) expressed by TAM,being able to quench phagocytosis. Interestingly,"Don't Eat Me" signal (DEMs) blockade with anti-CD47 monoclonal Antibody (mAb) showed promising activity in pretreated NHL,through increase of phagocytosis by TAM.CD24 was also demonstrated to be involved in DEMs in solid cancer.As a matter of fact, tumor-expressed CD24 promotes immune evasion through its interaction with the inhibitory receptor sialic-acid-binding Ig-like lectin10 (Siglec-10),expressed by TAM with immunosuppressive phenotype (M2-like).In a preclinical model of CD24+ solid tumors (ovarian and breast cancer) the blockade of CD24-Siglec-10 interaction with anti-CD24 mAb showed improvement of TAM-associated phagocytosis in vitro and TAM-dependent reduction of tumor growth and increase of survival in vivo.It is worth mentioning that CD24 can be expressed in some phases of B-cell differentiation and both MCL and CLL derives from a B-cell precursor with upregulated CD24.In this setting,CD24 might play a critical role in the anti-phagocytic signal, since MCL and CLL represents a subset of B-cell malignancies with a considerable hostile TME with M2-like TAM,able to jeopardize anti-cancer immunity.Therefore, the possibility to boost innate anti-cancer immunity through this DEMs blockade could provide new therapeutic options to previous heavily pretreated relapsed/refractory MCL and CLL patients.

Conditions

Mantle-cell Lymphoma; B Cell Chronic Lymphocytic Leukemia

Keywords

MCL; NHL; CLL; TAM

Outcome Measures

Primary Outcomes (1)

• Primary endopoint

  Rate of phagocytosis of human M2-like macrophages co-cultured with MCL and CLL blast cells treated with anti-CD24 mAb.

  36 months

Secondary Outcomes (1)

• Secondary endopoints

  36 months

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

This single-center will enroll approximately 30 patients suffering from MCL (n=10) and CLL (n=20) referred to the Department of Hematology at San Gerardo Hospital, Monza, Italy.

You may qualify if:

• Signed and dated EC-approved informed consent
• Diagnosis of Mantle-cell Lymphoma (MCL) or B-cell Chronic Lymphocytic Leukemia (CLL) defined according to World Health Organization (WHO) criteria.
• Female or male, 18 years of age or older.
• ECOG performance status 0-3.
• Willingness and ability to comply with routine clinical practice and study procedures.
• Signed and dated EC-approved informed consent.
• Healthy volunteers agreed to undergo plateletpheresis.
• Female or male, 18 years of age or older.
• Willingness and ability to comply with Transfusion Medicine clinical practice and study procedures.

You may not qualify if:

• Other hematological diseases defined by WHO criteria different from MCL and CLL.
• Previous treatment regimens that included allogeneic stem cell transplantation (ASCT).
• Healthy volunteers agreed to perform any kind of donations with the exception of plateletpheresis.

Sponsors & Collaborators

• University of Milano Bicocca: lead

Study Sites (1)

Andrea Aroldi

Monza, MB, 20900, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

peripheral blood and bone marrow blood

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Andrea Aroldi

  Ospedale San Gerardo - ASST Monza

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea Aroldi

CONTACT

+ 39 0392339065; andrea.aroldi@asst-monza.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2023
• First Posted: June 5, 2023
• Study Start: September 8, 2022
• Primary Completion: September 1, 2023
• Study Completion: December 1, 2024
• Last Updated: June 5, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)