Hypothesis: AdAPT-001 and pseudoprogression – when seeing is not necessarily believing

The purpose of this commentary is to highlight the high occurrence of clinical pseudoprogression and delayed responses that have been observed to date with the locally injected oncolytic adenovirus, AdAPT-001, currently in a Phase 1/2 clinical trial (NCT04673942) for the treatment of treatment-refra...

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Main Authors: Anthony Conley, Christopher Larson, Bryan Oronsky, Meaghan Stirn, Tony R Reid, Scott Caroen
Format: Article
Language:English
Published: BMJ Publishing Group 2024-06-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/12/6/e008809.full
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author Anthony Conley
Christopher Larson
Bryan Oronsky
Meaghan Stirn
Tony R Reid
Scott Caroen
author_facet Anthony Conley
Christopher Larson
Bryan Oronsky
Meaghan Stirn
Tony R Reid
Scott Caroen
author_sort Anthony Conley
collection DOAJ
description The purpose of this commentary is to highlight the high occurrence of clinical pseudoprogression and delayed responses that have been observed to date with the locally injected oncolytic adenovirus, AdAPT-001, currently in a Phase 1/2 clinical trial (NCT04673942) for the treatment of treatment-refractory tumors. Not surprisingly, these have led to confusion about response assessment and whether to continue patients on treatment. AdAPT-001 carries a transforming growth factor (TGF)-beta trap (TGF-β), which sequesters TGF-β, a cytokine that potently regulates inflammation, fibrosis, and immunosuppression in cancer. Pseudoprogression (PsP) or progression prior to response or stabilization, has been widely recognized with radiotherapy for primary brain tumors and immune checkpoint inhibitors (ICIs). PsP has also been described and documented in the context of oncolytic virotherapy but perhaps to a lesser extent. However, repeated intratumoral injections with these immunostimulatory agents may induce a more intense immune response and release more antigenic epitopes than with ICIs, for example, which are strictly T-cell directed rather than also tumor-directed like AdAPT-001.
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series Journal for ImmunoTherapy of Cancer
spelling doaj-art-0ebcfe55b7754f6895b2c5a7c3afe19a2025-08-20T03:07:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-06-0112610.1136/jitc-2024-008809Hypothesis: AdAPT-001 and pseudoprogression – when seeing is not necessarily believingAnthony Conley0Christopher Larson1Bryan Oronsky2Meaghan Stirn3Tony R Reid4Scott Caroen5Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA3EpicentRx, La Jolla, CA, USA3EpicentRx, La Jolla, CA, USA3EpicentRx, La Jolla, CA, USAEpicentRx Inc, La Jolla, California, USA4EpicentRx, San Diego, CA, USAThe purpose of this commentary is to highlight the high occurrence of clinical pseudoprogression and delayed responses that have been observed to date with the locally injected oncolytic adenovirus, AdAPT-001, currently in a Phase 1/2 clinical trial (NCT04673942) for the treatment of treatment-refractory tumors. Not surprisingly, these have led to confusion about response assessment and whether to continue patients on treatment. AdAPT-001 carries a transforming growth factor (TGF)-beta trap (TGF-β), which sequesters TGF-β, a cytokine that potently regulates inflammation, fibrosis, and immunosuppression in cancer. Pseudoprogression (PsP) or progression prior to response or stabilization, has been widely recognized with radiotherapy for primary brain tumors and immune checkpoint inhibitors (ICIs). PsP has also been described and documented in the context of oncolytic virotherapy but perhaps to a lesser extent. However, repeated intratumoral injections with these immunostimulatory agents may induce a more intense immune response and release more antigenic epitopes than with ICIs, for example, which are strictly T-cell directed rather than also tumor-directed like AdAPT-001.https://jitc.bmj.com/content/12/6/e008809.full
spellingShingle Anthony Conley
Christopher Larson
Bryan Oronsky
Meaghan Stirn
Tony R Reid
Scott Caroen
Hypothesis: AdAPT-001 and pseudoprogression – when seeing is not necessarily believing
Journal for ImmunoTherapy of Cancer
title Hypothesis: AdAPT-001 and pseudoprogression – when seeing is not necessarily believing
title_full Hypothesis: AdAPT-001 and pseudoprogression – when seeing is not necessarily believing
title_fullStr Hypothesis: AdAPT-001 and pseudoprogression – when seeing is not necessarily believing
title_full_unstemmed Hypothesis: AdAPT-001 and pseudoprogression – when seeing is not necessarily believing
title_short Hypothesis: AdAPT-001 and pseudoprogression – when seeing is not necessarily believing
title_sort hypothesis adapt 001 and pseudoprogression when seeing is not necessarily believing
url https://jitc.bmj.com/content/12/6/e008809.full
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AT tonyrreid hypothesisadapt001andpseudoprogressionwhenseeingisnotnecessarilybelieving
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