Phase 1 evaluation of APN401, an autologous CBL-B-silenced PBMC therapy, in advanced solid tumors
7 affiliations
- 1InvIOs GmbH, Campus Vienna Biocenter 5, 1030 Vienna, Austria
- 2Medical University of Vienna, Department of Transfusion Medicine and Cell Therapy, Waehringer Guertel 18-20, 1090 Vienna, Austria
- 3Medical University of Vienna, Department of Medicine I, Division of Oncology, Waehringer Guertel 18-20, 1090 Vienna, Austria
- 4Ordensklinikum Linz GmbH, Barmherzige Schwestern, Seilerstaette 4, 4020 Linz, Austria
- 5Medical University Innsbruck, Department of Internal Medicine V, Hematology and Oncology, Anichstrasse 35, 6020 Innsbruck, Austria
- 6Salzburg Cancer Research Institute, Center for Clinical Cancer and Immunology Trials, Paracelsus Medical University Salzburg, Muellner Hauptstrasse 48, 5020 Salzburg, Austria
- 7Austrian Red Cross, Blood Transfusion Service for Upper Austria, Krankenhaustrasse 7, 4010 Linz, Austria
Abstract
Intracellular immune checkpoints regulate activation thresholds in cytotoxic immune cells. Casitas B-lineage lymphoma proto-oncogene B (CBL-B) is an E3 ubiquitin ligase that negatively regulates antigen receptor signaling and T cell activation. APN401 is an autologous peripheral blood mononuclear cell (PBMC) therapy incorporating transient small interfering RNA (siRNA)-mediated CBL-B silencing. Two phase 1 studies evaluated escalating doses of APN401 in patients with advanced treatment-refractory solid tumors. APN401 was manufactured from leukapheresis-derived PBMCs using the EPiC point-of-care platform. Seventeen patients received APN401 across three dose levels. APN401 demonstrated a favorable safety profile, with no dose-limiting toxicities, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or grade ≥3 treatment-related adverse events. Manufacturing was reproducible across sites. Although no objective responses were observed, disease stabilization occurred in 5 of 10 Response Evaluation Criteria in Solid Tumors (RECIST)-evaluable patients (50.0%), corresponding to 29.4% of all 17 treated patients. Exploratory analyses identified treatment-associated systemic immune changes, including enrichment of circulating CD8⁺ T cells, induction of cytotoxic mediators, and expansion of dominant T cell receptor β (TCRβ) clonotypes. These changes were most pronounced in patients with stable disease but remain exploratory and hypothesis-generating. These findings support further evaluation of APN401 in larger, controlled studies.
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BibTeX
@article{dohnal2026phase,
title = {{Phase 1 evaluation of APN401, an autologous CBL-B-silenced PBMC therapy, in advanced solid tumors}},
author = {Alexander Dohnal and Nina Worel and Thomas Bogenrieder and Thorsten Fuereder and Martin Burian and Dominik Wolf and Gerald Prager and Richard Greil and Anja Peterbauer-Scherb and Beate Schrenk and Stefan Bunka and Ernesto Abila and Felix Batrina and Maria Urban and Julia Buchberger and Alice Schwarzboeck and Bernhard Peball and Sandra Seidl and Hannes Muehleisen and Stefan Stranner and Mario Kuttke and Angela Halfmann and Sarah Bischof and Andreas Birbach and Romana Gugenberger},
journal = {Molecular Therapy Oncology},
year = {2026},
month = oct,
doi = {10.1016/j.omton.2026.201357},
url = {https://europepmc.org/article/PMC/PMC13717735},
note = {CC BY},
}
RIS
TY - JOUR
TI - Phase 1 evaluation of APN401, an autologous CBL-B-silenced PBMC therapy, in advanced solid tumors
AU - Alexander Dohnal
AU - Nina Worel
AU - Thomas Bogenrieder
AU - Thorsten Fuereder
AU - Martin Burian
AU - Dominik Wolf
AU - Gerald Prager
AU - Richard Greil
AU - Anja Peterbauer-Scherb
AU - Beate Schrenk
AU - Stefan Bunka
AU - Ernesto Abila
AU - Felix Batrina
AU - Maria Urban
AU - Julia Buchberger
AU - Alice Schwarzboeck
AU - Bernhard Peball
AU - Sandra Seidl
AU - Hannes Muehleisen
AU - Stefan Stranner
AU - Mario Kuttke
AU - Angela Halfmann
AU - Sarah Bischof
AU - Andreas Birbach
AU - Romana Gugenberger
PY - 2026
DA - 2026/10/05
JO - Molecular Therapy Oncology
DO - 10.1016/j.omton.2026.201357
UR - https://europepmc.org/article/PMC/PMC13717735
AB - Intracellular immune checkpoints regulate activation thresholds in cytotoxic immune cells. Casitas B-lineage lymphoma proto-oncogene B (CBL-B) is an E3 ubiquitin ligase that negatively regulates antigen receptor signaling and T cell activation. APN401 is an autologous peripheral blood mononuclear cell (PBMC) therapy incorporating transient small interfering RNA (siRNA)-mediated CBL-B silencing. Two phase 1 studies evaluated escalating doses of APN401 in patients with advanced treatment-refractory solid tumors. APN401 was manufactured from leukapheresis-derived PBMCs using the EPiC point-of-care platform. Seventeen patients received APN401 across three dose levels. APN401 demonstrated a favorable safety profile, with no dose-limiting toxicities, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or grade ≥3 treatment-related adverse events. Manufacturing was reproducible across sites. Although no objective responses were observed, disease stabilization occurred in 5 of 10 Response Evaluation Criteria in Solid Tumors (RECIST)-evaluable patients (50.0%), corresponding to 29.4% of all 17 treated patients. Exploratory analyses identified treatment-associated systemic immune changes, including enrichment of circulating CD8⁺ T cells, induction of cytotoxic mediators, and expansion of dominant T cell receptor β (TCRβ) clonotypes. These changes were most pronounced in patients with stable disease but remain exploratory and hypothesis-generating. These findings support further evaluation of APN401 in larger, controlled studies.
SN - 2950-3299
ER -