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Abstract
Introduction. The development of novel anticancer drugs, including dendritic cell vaccines (DCVs), requires robust in vivo preclinical data. This underscores the need for biologically relevant animal models.
Aim. To assess the pharmacodynamics of the autologous dendritic cell-based vaccine CaTeVac (homologous dendritic cell vaccine, HDCV) using a novel in vivo model of transplantable murine spindle cell sarcoma 164 MSar FE (TSS).
Materials and Methods. In the preliminary study, tumor growth parameters and morphology were compared between autochthonous benzo(a)pyrene-induced sarcoma (BIS) and cultured TSS at passages 11, 40, and 72 in BALB/c mice (n = 110; 55 males, 55 females). In the main study, female BALB/c mice received: (1) prophylactic–therapeutic HDCV (PT-HDCV, n = 13; weekly for 4 weeks before and 4 weeks after TSS inoculation); (2) therapeutic HDCV (T-HDCV, n = 13; weekly for 4 weeks after inoculation); or (3) doxorubicin (DOX, n = 13; single intraperitoneal dose of 8 mg/kg 48 h after inoculation). Untreated mice served as controls (n = 12). Tumor size, response to therapy according to modified RECIST 1.1 criteria, time to progression (TTP), and overall survival (OS) were assessed.
Results. TSS at passage 72 was selected for further experiments because it retained BIS morphology while exhibiting synchronous tumor onset, a short latency period (7–9 days vs. 83 days for BIS), 100 % transplantability, and a 2.5-fold slower growth rate. Tumors reached target volume by days 11–14, compared to 3 months for BIS. In the main study, the PT-HDCV regimen induced an objective tumor response in 53.9 % of animals (p = 0.0052 vs. control), prolonged median TTP (63 days vs. 32 days in controls), and improved OS, with 3 out of 13 animals surviving without progression. The therapeutic HDCV regimen and doxorubicin were less effective.
Conclusion. A novel TSS model (164 MSar FE, passage 72) was characterized and validated, demonstrating the antitumor activity of a prophylactic–therapeutic HDCV regimen.
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