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

NCT ID: NCT07240207

Last Updated: 2025-11-20

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 44 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-01-19
• Study Completion Date: 2025-12-31

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

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• patients over 18
• non-solid malignancies

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role: lead

Responsible Party

Mirko Bertozzi

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Fondazione IRCCS Policlinico San Matteo, SC Chirurgia Pediatrica

Pavia, Pavia, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Mirko Bertozzi, MD

Role: CONTACT

m.bertozzi@smatteo.pv.it

+393393196807

Facility Contacts

Mirko bertozzi, MD

Role: primary

m.bertozzi@smatteo.pv.it

Other Identifiers

MOST

Identifier Type: -

Identifier Source: org_study_id