Heterologous prime-boost cellular vaccination induces potent antitumor immunity against triple negative breast cancer

被引:6
作者
Niavarani, Seyedeh-Raheleh [1 ]
St-Cyr, Guillaume [1 ]
Daniel, Lauren [1 ]
Lawson, Christine [1 ]
Giguere, Hugo [1 ]
Alkayyal, Almohanad A. [2 ,3 ]
Tai, Lee-Hwa [1 ,4 ]
机构
[1] Univ Sherbrooke, Dept Immunol & Cell Biol, Sherbrooke, PQ, Canada
[2] Univ Tabuk, Fac Appl Med Sci, Dept Med Lab Technol, Tabuk, Saudi Arabia
[3] King Abdullah Int Med Res Ctr, Immunol Res Program, Riyadh, Saudi Arabia
[4] Ctr Rech Ctr Hosp Univ Sherbrooke, Sherbrooke, PQ, Canada
来源
FRONTIERS IN IMMUNOLOGY | 2023年 / 14卷
基金
加拿大健康研究院;
关键词
Immunogenic cancer vaccine; oncolytic virotherapy; triple negative breast cancer; tumor microenvironment; immune effector cells; TUMOR-INFILTRATING LYMPHOCYTES; PHASE-II; IMMUNOTHERAPY; ADJUVANT; VACCINES; DISEASE; TRIALS; DEATH; CELLS;
D O I
10.3389/fimmu.2023.1098344
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
IntroductionTriple negative breast cancer (TNBC) is the most aggressive and hard-to-treat subtype of breast cancer, affecting 10-20% of all women diagnosed with breast cancer. Surgery, chemotherapy and hormone/Her2 targeted therapies are the cornerstones of treatment for breast cancer, but women with TNBC do not benefit from these treatments. Although the prognosis is dismal, immunotherapies hold significant promise in TNBC, even in wide spread disease because TNBC is infiltrated with more immune cells. This preclinical study is proposing to optimize an oncolytic virus-infected cell vaccine (ICV) based on a prime-boost vaccination strategy to address this unmet clinical need. MethodsWe used various classes of immunomodulators to improve the immunogenicity of whole tumor cells in the prime vaccine, followed by their infection with oncolytic Vesicular Stomatitis Virus (VSVd51) to deliver the boost vaccine. For in vivo studies, we compared the efficacy of a homologous prime-boost vaccination regimen to a heterologous strategy by treating 4T1 tumor bearing BALB/c mice and further by conducting re-challenge studies to evaluate immune memory responses in surviving mice. Due to the aggressive nature of 4T1 tumor spread (akin to stage IV TNBC in human patients), we also compared early surgical resection of primary tumors versus later surgical resection combined with vaccination. ResultsIn vitro results demonstrated that immunogenic cell death (ICD) markers and pro-inflammatory cytokines were released at the highest levels following treatment of mouse 4T1 TNBC cells with oxaliplatin chemotherapy and influenza vaccine. These ICD inducers also contributed towards higher dendritic cell recruitment and activation. With the top ICD inducers at hand, we observed that treatment of TNBC-bearing mice with the influenza virus-modified prime vaccine followed by VSVd51 infected boost vaccine resulted in the best survival. Furthermore, higher frequencies of both effector and central memory T cells along with a complete absence of recurrent tumors were observed in re-challenged mice. Importantly, early surgical resection combined with prime-boost vaccination led to improved overall survival in mice. ConclusionTaken together, this novel cancer vaccination strategy following early surgical resection could be a promising therapeutic avenue for TNBC patients.
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页数:13
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