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<p>Survivin, an anti-apoptotic protein, plays a pivotal role in cancer progression by disrupting the balance between cell division and apoptosis. We have developed and characterized an anti-Survivin vaccine designed as a triple fusion protein to enhance immunogenicity. In this study, we have evaluated the vaccine’s efficacy in reducing tumor growth using a Survivin expressing 4T1 pre-clinical mouse model of triple-negative breast cancer (TNBC), which is difficult to treat due to its heterogeneous microenvironment, aggressive nature, poor prognosis, and high relapse rates. The recombinant <sub>DC</sub>Survivin-LTB protein was purified, adsorbed onto alum, and formulated with <i>Mycobacterium indicus pranii</i> (MIP) before administration to Balb/c mice for dose optimization. The dose that maximized antibody production was selected for efficacy studies in 4T1 tumor-bearing mice in vivo. Vaccination elicited a strong anti-Survivin antibody response and significantly inhibited tumor growth compared with controls. Elevated Granzyme B levels in vaccinated mice indicated activation of the apoptotic pathway, contributing to tumor inhibition. IFN-γ, IL-2 and IL-12 levels were also higher after the vaccination which boosted the immune system to target the cancer cells. Histopathological analysis revealed no observable toxicity or adverse effects on major organs. Immunohistochemical analysis confirmed reduced expression of angiogenesis marker VEGF and increased expression of apoptotic marker Caspase 3. These findings highlight the potential of <sub>DC</sub>Survivin-LTB, in combination with MIP, as a promising immunotherapeutic approach for the treatment of metastatic TNBC expressing Survivin.</p>

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Survivin targeting triple-fusion vaccine DCSurvivin-LTB inhibits tumor growth in mouse model of triple-negative breast cancer

  • 期刊论文

  • 发表日期：

    2025年12月4日

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  • Ambreen Rashid,
  • Anuja Krishnan,
  • Sarika Gupta,
  • Jagdish C. Gupta,
  • G. P. Talwar

摘要

Survivin, an anti-apoptotic protein, plays a pivotal role in cancer progression by disrupting the balance between cell division and apoptosis. We have developed and characterized an anti-Survivin vaccine designed as a triple fusion protein to enhance immunogenicity. In this study, we have evaluated the vaccine’s efficacy in reducing tumor growth using a Survivin expressing 4T1 pre-clinical mouse model of triple-negative breast cancer (TNBC), which is difficult to treat due to its heterogeneous microenvironment, aggressive nature, poor prognosis, and high relapse rates. The recombinant DCSurvivin-LTB protein was purified, adsorbed onto alum, and formulated with Mycobacterium indicus pranii (MIP) before administration to Balb/c mice for dose optimization. The dose that maximized antibody production was selected for efficacy studies in 4T1 tumor-bearing mice in vivo. Vaccination elicited a strong anti-Survivin antibody response and significantly inhibited tumor growth compared with controls. Elevated Granzyme B levels in vaccinated mice indicated activation of the apoptotic pathway, contributing to tumor inhibition. IFN-γ, IL-2 and IL-12 levels were also higher after the vaccination which boosted the immune system to target the cancer cells. Histopathological analysis revealed no observable toxicity or adverse effects on major organs. Immunohistochemical analysis confirmed reduced expression of angiogenesis marker VEGF and increased expression of apoptotic marker Caspase 3. These findings highlight the potential of DCSurvivin-LTB, in combination with MIP, as a promising immunotherapeutic approach for the treatment of metastatic TNBC expressing Survivin.