Expansion of Tumor-infiltrating and Marrow-infiltrating Lymphocytes from Pediatric Malignant Solid Tumors

Overview

Journal Cytotherapy

Publisher Elsevier

Specialties Cell Biology
Pharmacology

Date 2024 Sep 7

PMID 39243253

Authors

Jonathan Metts

Madeline Rodriguez-Valentin

Jonathan Hensel

Alex Alfaro

Christopher W Snyder

Odion Binitie

Caroline Chebli

Hector Monforte

Shari Pilon-Thomas

John Mullinax

Affiliations

Soon will be listed here.

Abstract

Introduction: The expansion of tumor-infiltrating lymphocytes (TIL) for adoptive cellular therapy is under investigation in many solid tumors of adulthood. Marrow-infiltrating lymphocytes (MIL) have demonstrated antitumor reactivity preclinically. Successful expansion of TIL/MIL has not been reported across pediatric solid tumor histologies. The objective of this study was to demonstrate successful expansion of TIL from pediatric solid tumors for translation in an adoptive cell therapy (ACT) treatment strategy.

Methods: A prospective study of TIL/MIL expansion was performed on solid tumors of pediatric patients undergoing standard-of-care procedures. TIL/MIL expansions were performed in the presence of high-dose interleukin 2. To demonstrate a full-scale expansion to clinically-relevant cell doses for TIL therapy, initial TIL culture was followed by a rapid expansion protocol for select patients. Expanded specimens were analyzed for phenotype by flow cytometry and for anti-tumor reactivity by the interferon-gamma release assay.

Results: Eighteen tumor samples were obtained. Initial TIL cultures were successfully generated from 14/18 samples (77.7%). A median of 5.52 × 107 (range: 2.5 × 106-3.23 × 108) cells were produced from initial cultures, with 46.9% expressing a CD3 phenotype (46.9%). Eight samples underwent rapid expansion, demonstrating a median 458-fold expansion and a CD3 phenotype of 98%. Initial MIL cultures were successfully generated from five samples, with a predominantly CD3 phenotype (45.2%). Sufficient tumor tissue was only available for seven TIL samples to be tested for reactivity; none demonstrated responsiveness to autologous tumor.

Conclusions: TIL and MIL expansion from pediatric solid tumors was successful, including the full-scale expansion process. This data supports translation to an ACT-TIL treatment strategy in the pediatric population and thus a Phase I trial of ACT-TIL in pediatric high-risk solid tumors is planned.

Citing Articles

Adoptive Cellular Therapy for Pediatric Solid Tumors: Beyond Chimeric Antigen Receptor-T Cell Therapy.

Hensel J, Metts J, Gupta A, Ladle B, Pilon-Thomas S, Mullinax J Cancer J. 2022; 28(4):322-327.

PMID: 35880942 PMC: 9847472. DOI: 10.1097/PPO.0000000000000603.

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