Work

Vaccination Efficacy of Mitoxantrone-Treated CT-26 Cells Under Different Drug Concentrations and Vaccination Intervals

Year: 2026

Type: article

Abstract: Immunogenic cell death (ICD) converts dying tumor cells into an anticancer vaccine, yet whether protection depends on how those cells are prepared and when they are given has rarely been examined. Using mitoxantrone (MTX), a clinically approved small molecule classified as an ICD inducer, we examined both variables in the murine CT-26 colon carcinoma model. MTX reduced viability in a concentration-dependent manner and induced extracellular ATP release. The total extent of cell death, however, was similar across concentrations, indicating that the concentration-dependent loss of viability was not accompanied by a proportional increase in cell death. What differed was the composition of the dying population, which shifted from early to late apoptotic cells as the concentration increased. Prophylactic vaccination with MTX-treated cells protected BALB/c mice, leaving 75.0–87.5% of animals tumor-free after vaccination at 1 μM and 37.5–62.5% at 3 μM across independent experiments. Protection increased with the interval between vaccination and challenge, with 0%, 50.0%, and 87.5% of animals tumor-free after simultaneous injection, a 3-day interval, and a 7-day interval, respectively. Cells killed completely by freeze–thaw were inactive as a vaccine, and cisplatin-treated cells conferred only a marginal delay, whereas responders to MTX-treated cells resisted rechallenge for the remainder of the observation period. Taken together, these results show that use of an ICD-inducing drug alone is not sufficient for effective dying-cell vaccination and that protective efficacy is influenced by vaccine preparation and by the interval between vaccination and tumor challenge, rather than by the extent of cell death alone.

Source: Molecules

DOI: 10.3390/molecules31213827

Authors: Se Won Na, Mibae Jeong, Mi-Kyung Jeong, Jaemoo Chun

Institutions: Gyeongsang National University, Korea Institute of Oriental Medicine, Kyung Hee University, Korea University of Science and Technology

Language: English

Topic: Immunotherapy and Immune Responses

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258