Immunotherapy of Epstein-Barr Virus Associated Malignancies Using Mycobacterial HSP70 and LMP2A356–364 Epitope Fusion Protein

Liu, Genyan; Yao, Kun; Wang, Bing; Chen, Yun; Feng, Zijian; Guo, Yidi; Xu, Jin; Shi, Honglian

doi:10.1038/cmi.2009.54

Cited by 15 publications

(10 citation statements)

References 34 publications

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“…Using these transgenic mice overcomes the dual problem of human antigenic epitopes not binding to mouse MHC molecules and of mouse CD8 1 T cells not interacting with the a3 domain of human MHC molecules. 43 We investigated whether Her2-specific CTLs could be induced by immunization of HLA-A2.1/K b transgenic mice with BMDCs pulsed with Hsp70L1-Her2 341-456 . We demonstrated that the CTLs from these mice were able to lyse SW620 target cells and Her2-E75-pulsed T2 cells, showing stronger antigen-specific cytotoxicity than those generated from mice immunized with Her2 341-456 pulsed BMDCs.…”

Section: Discussionmentioning

confidence: 99%

Efficient induction of a Her2-specific anti-tumor response by dendritic cells pulsed with a Hsp70L1–Her2341–456 fusion protein

Fang

et al. 2011

Cell Mol Immunol

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Heat shock proteins (HSPs) have been shown to interact with antigen-presenting cells (APCs), especially dendritic cells (DCs). HSPs act as potent adjuvants, inducing a Th1 response, as well as antigen-specific CD8 1 cytotoxic T lymphocytes (CTL) via cross-presentation. Our previous work has demonstrated that Hsp70-like protein 1 (Hsp70L1), a new member of the Hsp70 subfamily, can act as a powerful Th1 adjuvant in a DC-based vaccine. Here we report the efficient induction of tumor antigen-specific T cell immune response by DCs pulsed with recombinant fusion protein of Hsp70L1 and Her2 341-456 , the latter of which is a fragment of Her2/neu (Her2) containing E75 (a HLA-A2 restricted CTL epitope). The fusion protein Hsp70L1-Her2 341-456 promotes the maturation of DCs and activates them to produce cytokines, such as IL-12 and TNF-a, and chemokines, such as MIP-1a, MIP-1b and RANTES. Taken together, these results indicate that the adjuvant activity of Hsp70L1 is maintained in the fusion protein.

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Section: Discussionmentioning

confidence: 99%

Efficient induction of a Her2-specific anti-tumor response by dendritic cells pulsed with a Hsp70L1–Her2341–456 fusion protein

Fang

et al. 2011

Cell Mol Immunol

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“…Antibody-based targeting immunotherapy is a wellestablished treatment for various tumor types, such as ErbB2-positive breast cancer (18), Hodgkin lymphoma, acute myeloid leukemia, colon cancer, lung cancer, melanoma, and some of head and neck squamous cell carcinomas (19)(20)(21)(22)(23)(24). Immunoconjugate therapy has not yet been applied to NPC, although some antigens have been found since many years ago to expresses at high levels on the surface of these tumor cells (25,26).…”

Section: Discussionmentioning

confidence: 99%

A Human Fab-Based Immunoconjugate Specific for the LMP1 Extracellular Domain Inhibits Nasopharyngeal Carcinoma Growth In Vitro and In Vivo

Chen

Zhang

Yuan

et al. 2012

Molecular Cancer Therapeutics

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Nasopharyngeal carcinoma (NPC) is a major cause of cancer-related death in Southeast Asia and China. Metastasis and relapse are the primary cause of morbidity and mortality in NPC. Recent evidence suggests that the Epstein-Barr virus latent membrane protein 1 (LMP1) is exclusively expressed in most NPC and is a potential target for biotherapy. In this study, we successfully prepared a novel human antibody Fab (HLEAFab) against LMP1 extracellular domain, which was subsequently conjugated with mitomycin C (MMC), thus forming an immunoconjugate (HLEAFab-MMC). The effects of HLEAFab-MMC on proliferation and apoptosis in NPC cell lines HNE2/LMP1 and the inhibition rate of growth of NPC xenografts in nude mice were examined. The inhibition rate of HNE2/LMP1 cell proliferation was the highest for HLEAFab-MMC (76%) compared with MMC (31%) and HLEAFab (22%) at a concentration of 200 nmol/L and showed dosedependent fashion. The apoptosis rate of HNE2/LMP1 cell lines was 13.88% in HLEAFab-MMC group, 3.04% in MMC group, 2.78% in HLEAFab group, and 2.10% in negative control group at the same concentration, respectively. In vivo, the inhibition rate of growth of NPC xenografts in nude mice was 55.1% in HLEAFab-MMC group, 26.5% in MMC group, and 5.64% in HLEAFab group. In summary, our findings show that HLEAFab-MMC is a unique immunoconjugate with the potential as a novel therapeutic agent in the treatment of LMP1-expressing NPC. Mol Cancer Ther; 11(3); 594-603. Ó2011 AACR.

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“…DNA encoding HSP70i-antigen fusion proteins was included in vaccines to melanoma (94). Such applications frequently use mycobacterial HSP70 (95). For anti-cancer vaccines, the use of xenogeneic stress proteins has the added advantage that nucleotide variations render the resulting protein increasingly immunogenic (mycobacterial and mouse HSP70 are approximately 50% homologous), whereas either version can bind peptides and proteins.…”

Section: Hsp70 Is a Star Player In Anti-tumor Vaccines And Treatment mentioning

confidence: 99%

A central role for inducible heat‐shock protein 70 in autoimmune vitiligo

Mosenson

Eby

Hernandez

et al. 2013

Experimental Dermatology

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Inducible Heat Shock Protein 70 (HSP70i) is a protein regulated by stress that protects cells from undergoing apoptosis. Such proteins are marvelously well conserved throughout evolution, which has placed them in the spotlight for helping to understand the intriguing relationship between infection and immunity. In the presence of stress proteins, dendritic cells (DCs) will sense this alarm signal and respond by recruiting immune cells of different plumage to fit the occasion. In times of stress, melanocytes will secrete antigen bound HSP70i to act as an alarm signal in activating DCs, that comes equipped with an address of origin to drive the autoimmune response in vitiligo. Here we pose that if the autoimmune response is funneled through HSP70i, then blocking the stress protein from activating DCs can lend new treatment opportunities for vitiligo.

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Immunotherapy of Epstein-Barr Virus Associated Malignancies Using Mycobacterial HSP70 and LMP2A356–364 Epitope Fusion Protein

Cited by 15 publications

References 34 publications

Efficient induction of a Her2-specific anti-tumor response by dendritic cells pulsed with a Hsp70L1–Her2341–456 fusion protein

Efficient induction of a Her2-specific anti-tumor response by dendritic cells pulsed with a Hsp70L1–Her2341–456 fusion protein

A Human Fab-Based Immunoconjugate Specific for the LMP1 Extracellular Domain Inhibits Nasopharyngeal Carcinoma Growth In Vitro and In Vivo

A central role for inducible heat‐shock protein 70 in autoimmune vitiligo

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