Dendritic Cells Pulsed with Cytokine-Adjuvanted Tumor Membrane Vesicles Inhibit Tumor Growth in HER2-Positive and Triple Negative Breast Cancer Models.
Dendritic Cells Pulsed with Cytokine-Adjuvanted Tumor Membrane Vesicles Inhibit Tumor Growth in HER2-Positive and Triple Negative Breast Cancer Models.
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DOI：
10.3390/ijms22168377
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发表时间：
2021-08-04
影响因子：
5.6
通讯作者：
Selvaraj P
中科院分区：
文献类型：
--
作者：
Munoz LE;Monterroza L;Bommireddy R;Shafizadeh Y;Pack CD;Ramachandiran S;Reddy SJC;Selvaraj P
树突状细胞（Dendritic cells，DC）是T细胞应答中最有效的抗原呈递细胞。迄今为止，FDA批准的唯一基于DC的免疫疗法是Sipuleucel-T，其利用融合蛋白用GM-CSF离体刺激DC，同时递送用于前列腺癌的抗原PAP。这种方法受到对单一抗原和具有确定的肿瘤相关抗原的癌症引起的免疫广度的限制。其他多抗原方法因疫苗佐剂功效差而受到限制。我们已经开发了一种疫苗平台，该疫苗平台由用从肿瘤组织制成的含精氨酸佐剂的肿瘤膜囊泡（TMV）脉冲的自体DC组成，所述TMV封装个体肿瘤的抗原景观。在这里，我们测试了与糖脂锚定的免疫刺激分子（GPI-ISMs）合并的TMV脉冲的DC在HER 2阳性和三阴性乳腺癌小鼠模型中的功效。用含有GPI-ISM的TMV脉冲DC导致囊泡的上级摄取、DC活化和细胞因子产生。TMV脉冲的DC适应性转移到荷瘤小鼠导致肿瘤生长的抑制、肺转移的减少和免疫细胞浸润到肿瘤中的增加。这些观察结果表明，可以进一步开发用含有GPI-GM-CSF和GPI-IL-12的TMV脉冲的DC，以用作癌症治疗的个性化免疫治疗平台。
Dendritic cells (DCs) are the most effective antigen presenting cells for the development of T cell responses. The only FDA approved DC-based immunotherapy to date is Sipuleucel-T, which utilizes a fusion protein to stimulate DCs ex vivo with GM-CSF and simultaneously deliver the antigen PAP for prostate cancer. This approach is restricted by the breadth of immunity elicited to a single antigen, and to cancers that have a defined tumor associated antigen. Other multi-antigen approaches have been restricted by poor efficacy of vaccine adjuvants. We have developed a vaccine platform that consists of autologous DCs pulsed with cytokine-adjuvanted tumor membrane vesicles (TMVs) made from tumor tissue, that encapsulate the antigenic landscape of individual tumors. Here we test the efficacy of DCs pulsed with TMVs incorporated with glycolipid-anchored immunostimulatory molecules (GPI-ISMs) in HER2-positive and triple negative breast cancer murine models. Pulsing of DCs with TMVs containing GPI-ISMs results in superior uptake of vesicles, DC activation and cytokine production. Adaptive transfer of TMV-pulsed DCs to tumor bearing mice results in the inhibition of tumor growth, reduction in lung metastasis, and an increase in immune cell infiltration into the tumors. These observations suggest that DCs pulsed with TMVs containing GPI-GM-CSF and GPI-IL-12 can be further developed to be used as a personalized immunotherapy platform for cancer treatment.
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影响因子：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.
影响因子：
5.8
作者：
Ebrahimi-Nik, Hakimeh;Corwin, William L.;Srivastava, Pramod K.
通讯作者：
Srivastava, Pramod K.
影响因子：
3.9
作者：
Kavanagh, Brian;Ko, Andrew;Fong, Lawrence
通讯作者：
Fong, Lawrence
DOI：
10.1177/0394632017711055
发表时间：
2017-06
影响因子：
3.5
作者：
Ma N;Liu Q;Hou L;Wang Y;Liu Z
通讯作者：
Liu Z
癌症免疫疗法。树突状细胞疫苗增加了黑色素瘤新抗原特异性T细胞的广度和多样性。
DOI：
10.1126/science.aaa3828
发表时间：
2015-05-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Carreno BM;Magrini V;Becker-Hapak M;Kaabinejadian S;Hundal J;Petti AA;Ly A;Lie WR;Hildebrand WH;Mardis ER;Linette GP
通讯作者：
Linette GP