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Fast tumor-infiltrating lymphocytes (TILs) for treatment of metastatic cancer with malignant pleural effusion: Protocol for the phase I regional immuno-oncology trial (RIOT)-4
Journal article   Open access

Fast tumor-infiltrating lymphocytes (TILs) for treatment of metastatic cancer with malignant pleural effusion: Protocol for the phase I regional immuno-oncology trial (RIOT)-4

Patrick L. Wagner, Catherine R. Lewis, Paige O. Mirsky, Oleksii Kucherenko, Christopher Sherry, Brett M. Szeligo, Shannon Altpeter, Samantha Devine, Vera S. Donnenberg, Neda Dadgar, …
Surgical oncology insight, v 3(3), 100277
Sep 2026
Featured in Collection :   Drexel's Newest Publications
url
https://doi.org/10.1016/j.soi.2026.100277View
Published, Version of Record (VoR) Open

Abstract

Adoptive cellular therapy CliniMACS Prodigy Malignant pleural effusions Pleural infiltrating T cells TILs
Malignant pleural effusions (MPE) are a manifestation of advanced malignancy associated with poor prognosis, limited survival, and significant symptom burden. Current management is largely palliative and focused on fluid control rather than disease-modifying regional therapy. Malignant pleural effusions frequently contain abundant pleural infiltrating T (PIT) cells, representing an accessible and clinically feasible starting material for rapid autologous adoptive cellular therapy (ACT). RIOT-4 is a single-center, Phase I translational feasibility and safety clinical trial evaluating intrapleural administration of a locally manufactured PIT-derived ACT product generated using a closed GMP-compliant CliniMACS Prodigy® platform. The primary objective is to evaluate the safety and feasibility of intrapleural administration of a locally manufactured Fast TIL product in combination with low-dose intrapleural interleukin-2 (IL-2). Secondary objectives include ACT product characterization, immune profiling of pleural fluid and peripheral blood, T cell receptor (TCR) repertoire dynamics, cytokine/secretome analysis, spatial immune mapping, and preliminary clinical response assessment. This trial leverages institutional GMP cellular therapy infrastructure to generate a rapid, autologous Fast TIL product from pleural effusion as a novel compartmental immunotherapy strategy for patients with malignant pleural disease.

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