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This includes mathematical modeling of CAR T cells, a modality of cancer therapy by which genetically engineered immune cells recognize and combat a cancerous target. While successful against hematologic malignancies, CAR T cells have shown limited success against other cancer types. Thus, more research is needed to understand their mechanisms of action and leverage their full potential. In our work, we set out to apply information theory on a mathematical model of NF\u03baB signaling initiated by the CAR following antigen encounter. First, we estimated channel capacity for CAR-4-1BB-mediated NF\u03baB signal transduction. Next, we evaluated the pathway\u2019s ability to distinguish contrasting \u201clow\u201d and \u201chigh\u201d antigen concentration levels, depending on the amount of variability in protein concentrations. Finally, we assessed the fidelity by which NF\u03baB activation reflects the encountered antigen concentration, depending on the prevalence of antigen-positive targets in tumor population. We found that in most scenarios, fold change in the nuclear concentration of NF\u03baB carries a higher channel capacity for the pathway than NF\u03baB\u2019s absolute response. Additionally, we found that most errors in transducing the antigen signal through the pathway skew towards underestimating the concentration of encountered antigen. Finally, we found that disabling IKK\u03b2 deactivation could increase signaling fidelity against targets with antigen-negative cells. Our information-theoretic analysis of signal transduction can provide novel perspectives on biological signaling, as well as enable a more informed path to cell engineering.<\/jats:p>","DOI":"10.1007\/s11538-023-01232-6","type":"journal-article","created":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T07:02:51Z","timestamp":1701414171000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Information-Theoretic Analysis of a Model of CAR-4-1BB-Mediated NF\u03baB Activation"],"prefix":"10.1007","volume":"86","author":[{"given":"Vardges","family":"Tserunyan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6901-3692","authenticated-orcid":false,"given":"Stacey","family":"Finley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,12,1]]},"reference":[{"issue":"5","key":"1232_CR1","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1016\/j.immuni.2021.04.011","volume":"54","author":"A Adelaja","year":"2021","unstructured":"Adelaja A, Taylor B, Sheu KM, Liu Y, Luecke S, Hoffmann A (2021) Six distinct NF\u03baB signaling codons convey discrete information to distinguish stimuli and enable appropriate macrophage responses. 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