Dissecting Tumour MicroenvirOnment in Solid Paediatric Tumour to Improve Adoptive Cell Therapy

NCT07240207 | Recruiting

• 1 other identifier: MOST
• Study Type: observational
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Pediatric solid tumors exhibit a low mutational burden, limited availability of neoantigens, and poor infiltration of tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment (TME), characteristics that reduce the effectiveness of immunotherapies in children. However, pediatric tumors express a subgroup of antigens that can be exploited as targets. Stimulating the T lymphocyte response against these antigens could overcome immunosuppressive barriers. The adoption of therapies based on cytotoxic T lymphocytes (CTLs) represents a promising strategy. A total of 42 neoplasms were analyzed, including: 8 neuroblastomas, 7 sarcomas, 4 nephroblastomas, 1 renal carcinoma, 2 rhabdomyosarcomas, 5 lymphomas, 2 ovarian carcinomas, 4 teratomas, 2 thyroid tumors, and 7 other rare tumors. Primary cells from these tumors were preserved, resulting in the stabilization of 5 cell lines used for functional studies in vitro. Currently, 4 tumor-specific CTL lines derived from healthy adult donors have been expanded; tumor antigen-specific T cells showed the ability to recognize and kill commercial tumor cell lines as well as stabilized pediatric tumor lines from osteosarcoma, nephroblastoma, and neuroblastoma. In particular, the G-Rex bioreactor enabled greater expansion of CTLs while maintaining a broad spectrum of specificity for most tumor antigens and a lymphocyte phenotype with an increased composition of early memory T cells, correlated with greater persistence in vivo. The results demonstrate that the use of bioreactors represents a significant advancement in the production of CTLs specific for pediatric tumor antigens. The ability of CTLs derived from bioreactors to express early memory and activation markers makes them particularly promising for clinical applications, where persistence and efficacy are key factors. Based on the presented results, the analysis of in vivo persistence and cytotoxic capacities in preclinical models will be deepened, aiming to confirm the efficacy of the produced cells. The main objective of the project is to develop expansion protocols for CTLs specific to pediatric tumor antigens, proposing innovative protocols for the ex vivo expansion of CTLs targeting pediatric tumor antigens. Finally, standardizing the large-scale process could be another necessary objective to translate these findings into practical clinical applications improving immunotherapy in pediatric cancer with evident benefits for affected children and care givers.

Conditions

Pediatric Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Cytotoxic Activity of Expanded CTLs Against Pediatric Tumor Cell Lines In Vitro

  Cytotoxic activity of tumor antigen-specific cytotoxic T lymphocytes (CTLs) expanded using G-Rex bioreactors will be measured by quantifying target cell lysis using a standard chromium-51 release assay or flow cytometry-based killing assay against stabilized pediatric tumor cell lines, including neuroblastoma, nephroblastoma, and osteosarcoma.

  Days 7, 14, and 21 post-CTL expansion

Eligibility Criteria

• Age: 1 Day - 18 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Pediatric patients affected by solid tumors enrolled for treatment at Fondazione IRCCS Policlinico San Matteo, pavia, Italy in the period 2023-2025

You may qualify if:

• pediatric patients 0-18 years
• affected by solid tumors

You may not qualify if:

• patients over 18
• non-solid malignancies

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead

Study Sites (1)

Fondazione IRCCS Policlinico San Matteo, SC Chirurgia Pediatrica

Pavia, Pavia, 27100, Italy

RECRUITING

Central Study Contacts

Mirko Bertozzi, MD

CONTACT

+393393196807; m.bertozzi@smatteo.pv.it

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 11, 2025
• First Posted: November 20, 2025
• Study Start: January 19, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: November 20, 2025

Record last verified: 2025-08

Locations

IT (1)