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Life sciences · Journal article
Kinases and Phosphatases · August 18, 2026
Early or partial results. Treat as a signal, not a conclusion.
This is an early mechanistic investigation showing that CIGB-300, a CK2-inhibiting peptide, induces extracellular HMGB-1 release in most of 18 cancer cell lines in vitro (p = 0.01) and in 4 of 7 blood cancer patients in a Phase I trial. The finding is preliminary evidence that CIGB-300 may trigger immunogenic cell death markers, but the clinical significance and context-dependency (variable response in NSCLC) require confirmation in larger, controlled studies.
In vitro multi-cell-line study combined with open-label Phase I exploratory cohort. In vitro: 18 cancer cell lines from blood malignancies, uterine-cervical cancer, and NSCLC. In vivo: blood cancer patients enrolled in Phase I study.. Intervention: CIGB-300 peptide (CK2 kinase inhibitor) at IC50 dose in vitro; CIGB-300 treatment in Phase I trial..
CIGB-300 upregulated HMGB-1 in culture supernatant of most cell lines at IC50 dose over 24 h (p = 0.01) Fold-change increases ≥2 in HMGB-1 were associated with intrinsic cell line sensitivity to CIGB-300 cytotoxicity Response was context-specific: clear induction in blood and cervical cancer cells, diffuse pattern in NSCLC
Fold-change increases ≥2 in HMGB-1 were associated with intrinsic cell line sensitivity to CIGB-300 cytotoxicity
HMGB-1 release may be explored as a response biomarker for CIGB-300, but the inconsistent induction across tumour types and very small Phase I cohort mean this finding is not yet actionable for clinical decision-making. Further investigation in larger, controlled trials is needed to establish whether HMGB-1 correlates with clinical benefit.
Early mechanistic work combining in vitro cell lines with exploratory Phase I data, investigating a biomarker association rather than clinical outcomes; needs confirmatory studies in larger patient cohorts.
As stated by the source record.
Quoted from the source exactly as published.
HMGB-1 release may be explored as a response biomarker for CIGB-300, but the inconsistent induction across tumour types and very small Phase I cohort mean this finding is not yet actionable for clinical decision-making. Further investigation in larger, controlled trials is needed to establish whether HMGB-1 correlates with clinical benefit.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
HMGB-1 is an alarmin representative of DAMP playing a central role in immunogenic cell death (ICD), a necessary condition in the dialog established between dying tumor cells and the immune system during some anticancer therapies. Therefore, early screening for ICD inducers represents a major priority in drug development today. In this work, we investigated the effect elicited by the clinical-grade CIGB-300 peptide, which impairs Protein Kinase CK2-mediated phosphorylation and other CK2 signaling connected kinases. Here, HMGB-1 extracellular release was investigated in an 18-cell line panel from blood malignancies, uterine-cervical cancer and NSCLC treated with CIGB-300 at equipotent doses (IC50) over 24 h. Interestingly, CIGB-300 treatment upregulated the HMGB-1 protein levels at the culture supernatant in most of the cell lines (p = 0.01) and fold-change increases ≥ 2 were associated with intrinsic cell line sensitivity towards CIGB-300’s cytotoxic effect. However, the HMGB-1 release by CIGB-300 was context-specific with clear induction on blood and uterine-cervical cancer cells and a diffused response pattern in NSCLC. Importantly, CIGB-300 treatment of blood cancer patients enrolled in a Phase I study induced plasma HMGB-1 alarmin in 4 out of 7 subject who received the entire treatment plan. Altogether, our data reveal for the first time that CIGB-300 treatment is able to induce extracellular HMGB-1 release in vitro and in vivo which could be indicative of ICD induction in some kinds of tumors; furthermore, the induction of extracellular HMGB-1 alarmin as a putative CIGB-300 response biomarker merits further investigation.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.