Dissecting Tumour MicroenvirOnment in Solid Paediatric Tumour to Improve Adoptive Cell Therapy (MOST)
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.
Study Overview
Status
Conditions
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Mirko Bertozzi, MD
- Phone Number: +393393196807
- Email: m.bertozzi@smatteo.pv.it
Study Locations
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Pavia
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Pavia, Pavia, Italy, 27100
- Recruiting
- Fondazione IRCCS Policlinico San Matteo, SC Chirurgia Pediatrica
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Contact:
- Mirko bertozzi, MD
- Email: m.bertozzi@smatteo.pv.it
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- pediatric patients 0-18 years
- affected by solid tumors
Exclusion Criteria:
- patients over 18
- non-solid malignancies
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Cytotoxic Activity of Expanded CTLs Against Pediatric Tumor Cell Lines In Vitro
Time Frame: Days 7, 14, and 21 post-CTL expansion
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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.
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Days 7, 14, and 21 post-CTL expansion
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- MOST
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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