New Preclinical and Clinical Approaches to Mesothelioma

Marco Emilio Bianchi70 enrolled

Overview

This study protocol involves the coordination between UO1 (IRCCS San Raffaele Hospital) and UO2 (Istituto Nazionale Tumori di Napoli - IRCCS G. Pascale) to explore the role of HMGB1 and CXCR4 in cancer treatment and metastasis. UO1 focuses on the role of HMGB1 in inflammation, mesothelioma progression, and tissue repair, as well as developing, in future, possible HMGB1 inhibitors for cancer therapy. UO2 specializes in CXCR4's role in cancer, developing CXCR4 antagonists, and tracking CXCR4-dependent metastasis. The hypothesis is that targeting HMGB1 and CXCR4 pathways will inhibit tumor progression and metastasis, enhancing anti-tumor immunity and improving therapeutic outcomes in cancer.

This is a multicentric cross-sectional observational study with an additional blood volume collected during blood sampling performed for normal clinical practice. The enrollment will take

Study Type

OBSERVATIONAL

Enrollment

Conditions

Mesothelioma

Eligibility

Sex: ALL

Medical Language ↔ Plain English

Inclusion Criteria: * Patients with Mesothelioma: Clinical suspicion or histologically confirmed diagnosis of pleural mesothelioma. * Candidates for surgical intervention. * Age 18 years or older. It is possible to include both male and female patients, male and female patients of reproductive age, as well as breastfeeding women. * Capacity to comprehend the study nature and provide autonomously informed consent. Control Group patients: * Absence of pleural mesothelioma but presence of other histologically confirmed diseases (neoplastic, inflammatory, or infectious). * Candidates for surgical intervention. * Age 18 years or older. It is possible to include both male and female patients, male and female patients of reproductive age, as well breastfeeding women. * Ability to understand the study nature and provide autonomously informed consent. If the patient's diagnosis, whether provisional or definitive, does not confirm the clinical suspicion, they will not undergo further evaluation in the study. Exclusion Criteria: * Lack of biopsy material. * pregnancy. * Unwillingness to sign the Informed Consent.

Outcomes

Primary Outcomes

To set up spheroids models to study and serve as a platform

Number of spheroids with infiltrated macrophages. About of 30% of macrophages infiltrated into spheroids.

Time frame: 0/baseline

To set up spheroids models and serve as a platform

Evaluation of macrophages polarization status M1 or M2 based on different genes and proteins expression using qPCR and Flow Cytometry.

Time frame: 0/baseline

To set up organoid models

Number of organoids formation. About of 30% of biopsies generated organoids.

Time frame: 0/baseline

Test inhibitors on spheroids and organoids and assess the response of individual patients to therapy

Rate of growth to test the efficacy of anti-CSF1R, BoxA and DFL using human mesospheres from MPM primary cell lines derived from patients and monocytes from controls.

Time frame: 0/baseline

Secondary Outcomes

To investigate inhibitors of the CXCR4-CXCL12-HMGB1 axis on the crosstalk

Percentage of migrated or invaded MPM cell lines NCI-H2052 (BAP1 WT/NF2 MUT) vs NCI-H28 (BAP1 mut/NF2 WT) with and without macrophages in presence of CDDP-Nivolumab (NIVO)-Peptide R54.

Time frame: 0/baseline

To investigate inhibitors of the CXCR4-CXCL12-HMGB1 axis on the crosstalk

Percentage of cell death of Tregs/Macrophages from peripheral blood and pleural effusion derived from MPM patients treated with and without R54.

Time frame: 0/baseline

To investigate inhibitors of the CXCR4-CXCL12-HMGB1 axis on the crosstalk

Overall survival of mice with MPM treated with CDDP-anti-PD-1/R54.

Time frame: In vivo experiment 3 weeks.

New Preclinical and Clinical Approaches to Mesothelioma

Overview

Conditions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts