Objective response after immune checkpoint inhibitors in a chemotherapy-refractory pMMR/MSS metastatic rectal cancer patient primed with experimental AlloStim® immunotherapy

Background Immune Checkpoint Inhibitor (ICI) immunotherapy is most effective in immune effector cell infiltrated 'hot' tumor lesions, such as occurs in deficient mismatch repair, microsatellite instability high (dMMR/MSI-H) colorectal cancer (CRC). However, most all metastatic CRC tumors a...

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Veröffentlicht in:Translational Medicine Communications 2024-05, Vol.9 (1), p.1-11, Article 15
Hauptverfasser: Hirschfeld, Ariel, Gurell, Daniel, Har-Noy, Michael
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Sprache:eng
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Zusammenfassung:Background Immune Checkpoint Inhibitor (ICI) immunotherapy is most effective in immune effector cell infiltrated 'hot' tumor lesions, such as occurs in deficient mismatch repair, microsatellite instability high (dMMR/MSI-H) colorectal cancer (CRC). However, most all metastatic CRC tumors are mismatch repair proficient/microsatellite stable (pMMR/MSS) 'cold' lesions, without significant immune cell infiltration, and are unresponsive to ICI. AlloStim[R], is an experimental, allogeneic immunomodulatory cell therapy designed to convert 'cold' metastatic tumor lesions to 'hot' inflamed lesions. After AlloStim[R] immunotherapy, this cold to hot inflammatory mechanism can make it difficult to distinguish between pseudoprogression and actual progression on restaging CT scans, as inflamed metastatic lesions can appear larger and occult disease can appear as new small lesions. Methods To explore whether radiological progression after AlloStim[R] immunotherapy is due to immune-flare or disease progression, we administered a short course of a combination ICI therapy to a pMMR/MSS chemotherapy-refractory metastatic colorectal cancer patient enrolled in the StimVax Phase IIb clinical study that presented with radiological progression after AlloStim[R] immunotherapy. Our rationale was that an accelerated response to ICI should occur if the lesions were inflamed, while if the enlarged lesions were due to disease progression there would not be a response. Results Here we report a rapid, significant reduction in tumor burden in response to ICI administration in an AlloStim[R] primed pMMR/MSS mCRC patient with retroperitoneal and lung metastases. Conclusion This rare objective response to ICIs in a pMMR/MSS mCRC patient supports further evaluation of the combination of AlloStim[R] with ICI immunotherapy in MSS mCRC and other cold or ICI refractory tumors. Trial registration National Library of Medicine (NLM) at the National Institutes of Health (NIH). Registered 22 June 2020, Keywords: Immunotherapy, Metastatic colorectal cancer, Microsatellite stable, Checkpoint inhibitor
ISSN:2396-832X
2396-832X
DOI:10.1186/s41231-024-00174-y