scholarly journals EGFR-targeting, β-defensin-tailored fusion protein exhibits high therapeutic efficacy against EGFR-expressed human carcinoma via mitochondria-mediated apoptosis

2018 ◽  
Vol 39 (11) ◽  
pp. 1777-1786 ◽  
Author(s):  
Wen-Juan Liu ◽  
Xiu-Jun Liu ◽  
Jian Xu ◽  
Liang Li ◽  
Yi Li ◽  
...  
PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e31908 ◽  
Author(s):  
Shanmin Zhao ◽  
Yong Zhao ◽  
Fengfeng Mao ◽  
Caiqin Zhang ◽  
Bing Bai ◽  
...  

2018 ◽  
Vol 102 (20) ◽  
pp. 8895-8907 ◽  
Author(s):  
Soumya Paul ◽  
Bhavani V. Peddayelachagiri ◽  
Sowmya Nagaraj ◽  
Balakrishna Konduru ◽  
Harsh V. Batra

Vaccine ◽  
2019 ◽  
Vol 37 (22) ◽  
pp. 2915-2924 ◽  
Author(s):  
Diane M. Da Silva ◽  
Joseph G. Skeate ◽  
Elena Chavez-Juan ◽  
Kim P. Lühen ◽  
Jiun-Ming Wu ◽  
...  

2020 ◽  
Vol 28 (8) ◽  
pp. 1806-1817
Author(s):  
Zhan Li ◽  
Yuqing Song ◽  
Peisong Yuan ◽  
Wei Guo ◽  
Xueting Hu ◽  
...  

2020 ◽  
Vol 16 (7) ◽  
pp. 1119-1134
Author(s):  
Yangzi Li ◽  
Xiaomei Yang ◽  
Xiaoling Lu ◽  
Zhengui Peng ◽  
Chunhui Lai ◽  
...  

In this research, we studied the therapeutic efficacy of a newly designed fusion protein containing Endoglin single-chain variable fragment and IP10 (Endoglin-scFv/IP10), together with our recently generated TRP2-specific CD8+ CD28+ CTLs (CD8+ CD28+ CTLs) in controlling melanoma growth in mice. The recombinant Endoglin-scFv/IP10 was expressed in E. coli, purified by affinity chromatography, and characterized in vitro for its chemotactic movement and immunoreactivity with endoglin-expressing cells. In vivo, melanoma xenografts were established in mice (C57BL/6) using B16F10 cells. After that, mice were treated with intravenous injections of vehicle (PBS), Endoglin-scFv/IP10 alone, CD8+ CD28+ CTLs alone, or Endoglin-scFv/IP10+ CD8+ CD28+ CTLs. The therapeutic efficacy was assessed by monitoring tumor growth, mouse survival and cellular biomarkers. Endoglin-scFv/IP10 fusion protein combined with CD8+ CD28+ CTLs observed a reduction in tumor growth, resulting in improved survival. On the cellular level, the combination treatment dramatically reduced the number of systemic and tumor associated myeloid-derived suppressor cells or regulatory T cells, increased tumor-responsive interferon-γ-producing lymphocytes and tumor-associated CD8+ CXCR3+ T cells, and inhibited proliferation and angiogenesis but stimulated apoptosis within melanoma tissue. This study demonstrates the therapeutic potential of Endoglin-scFv/IP10 fusion protein in combination with CD8+ CD28+ CTLs in melanoma treatment.


Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 914 ◽  
Author(s):  
Backhaus ◽  
Veinalde ◽  
Hartmann ◽  
Dunder ◽  
Jeworowski ◽  
...  

Tumor-targeted immunomodulation using oncolytic viral vectors is currently being investigated as a promising strategy in cancer therapy. In a previous study, we showed that a measles virus Schwarz vaccine strain (MeVac) vector encoding an interleukin-12 fusion protein (FmIL-12) is an effective immunotherapy in the MC38cea murine colon adenocarcinoma model. We hypothesized that MeVac encoding interleukin-15 may mediate enhanced T and NK cell responses and thus increase the therapeutic efficacy, especially in NK cell-controlled tumors. Therefore, we generated MeVac vectors encoding an interleukin-15 superagonist, FmIL-15. Replication and oncolytic capacity, transgene expression, and functionality of MeVac FmIL-15 vectors were validated in vitro. Effects on the tumor immune landscape and therapeutic efficacy of both FmIL-12 and FmIL-15 vectors were studied in the MC38cea and B16hCD46 tumor models. Treatment with MeVac FmIL-15 increased T and NK cell infiltration in both models. However, MeVac FmIL-12 showed more robust viral gene expression and immune activation, resulting in superior anti-tumor efficacy. Based on these results, MeVac encoding a human IL-12 fusion protein was developed for future clinical translation.


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