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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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2024-06-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/6/e008809.full |
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| _version_ | 1849736870159712256 |
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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. |
| format | Article |
| id | doaj-art-0ebcfe55b7754f6895b2c5a7c3afe19a |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-06-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| 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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