Microbial HSP70 peptide epitope 407–426 as adjuvant in tumor-derived autophagosome vaccine therapy of mouse lung cancer

Li, Jian; Xing, Yun; Zhou, Zhansong; Yao, Wenjun; Cao, Ruihua; Li, Taiming; Xu, Maolei; Wu, Jie

doi:10.1007/s13277-016-5309-2

Cited by 10 publications

(5 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies using mouse models have shown that HSP70 can be used as an adjuvant in cancer vaccine development strategies [45,46]. HSPs have therefore been harnessed as adjuvants of vaccines against cancers and infectious diseases [47]: examples include Phase I clinical trials for Glioblastoma (HSP70), colon carcinoma, Phase I-II studies for Non-small cell lung carcinoma (HSP70-activated NK cells) and a Phase I HIV vaccine study [25].…”

Section: Discussionmentioning

confidence: 99%

Impact of a Heat Shock Protein Impurity on the Immunogenicity of Biotherapeutic Monoclonal Antibodies

et al. 2019

View full text Add to dashboard Cite

Purpose Anti-drug antibodies can impair the efficacy of therapeutic proteins and, in some circumstances, induce adverse health effects. Immunogenicity can be promoted by aggregation; here we examined the ability of recombinant mouse heat shock protein 70 (rmHSP70) - a common host cell impurity - to modulate the immune responses to aggregates of two therapeutic mAbs in mice. Methods Heat and shaking stress methods were used to generate aggregates in the sub-micron size range from two human mAbs, and immunogenicity assessed by intraperitoneal exposure in BALB/c mice. Results rmHSP70 was shown to bind preferentially to aggregates of both mAbs, but not to the native, monomeric proteins. Aggregates supplemented with 0.1% rmHSP70 induced significantly enhanced IgG2a antibody responses compared with aggregates alone but the effect was not observed for monomeric mAbs. Dendritic cells pulsed with mAb aggregate showed enhanced IFNγ production on co-culture with T cells in the presence of rmHSP70. Conclusion The results indicate a Th1-skewing of the immune response by aggregates and show that murine rmHSP70 selectively modulates the immune response to mAb aggregates, but not monomer. These data suggest that heat shock protein impurities can selectively accumulate by binding to mAb aggregates and thus influence immunogenic responses to therapeutic proteins. Electronic supplementary material The online version of this article (10.1007/s11095-019-2586-7) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Impact of a Heat Shock Protein Impurity on the Immunogenicity of Biotherapeutic Monoclonal Antibodies

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Fusion diphtheria toxin (DT) and two tandem repeats of HSP70 407-426 with TCLs elicit strong humoral and cellular immune responses, leading to the growth inhibition of breast cancer (178). In addition, a tumor-derived autophagosome (Dribble) vaccine conjugated with HSP70 407-426 significantly induced a higher expression of antigen-specific cytotoxic T lymphocytes (CTLs) (179). Genetic vaccines encompass DNA or RNA vaccines delivered by viruses or plasmids.…”

Section: Developing Hsp70-based Vaccinesmentioning

confidence: 99%

Diversity of extracellular HSP70 in cancer: advancing from a molecular biomarker to a novel therapeutic target

Hu,

Liu,

Zhao

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

Heat shock protein 70 (HSP70) is a highly conserved protein functioning as a “molecular chaperone”, which is integral to protein folding and maturation. In addition to its high expression within cells upon stressful challenges, HSP70 can be translocated to the cell membrane or released from cells in free form or within extracellular vesicles (EVs). Such trafficking of HSP70 is also present in cancer cells, as HSP70 is overexpressed in various types of patient samples across a range of common malignancies, signifying that extracellular HSP70 (eHSP70) can serve as a tumor biomarker. eHSP70 is involved in a broad range of cancer-related events, including cell proliferation and apoptosis, extracellular matrix (ECM) remodeling, epithelial-mesenchymal transition (EMT), angiogenesis, and immune response. eHSP70 can also induce cancer cell resistance to various treatments, such as chemotherapy, radiotherapy, and anti-programmed death-1 (PD-1) immunotherapy. Though the role of eHSP70 in tumors is contradictory, characterized by both pro-tumor and anti-tumor effects, eHSP70 serves as a promising target in cancer treatment. In this review, we comprehensively summarized the current knowledge about the role of eHSP70 in cancer progression and treatment resistance and discussed the feasibility of eHSP70 as a cancer biomarker and therapeutic target.

show abstract

“…Some HSP70-based vaccines were designed to enhance the antigen-presenting capacity of DCs to T cells based on the results that HSP70 promoted DCs maturation, upregulation of co-stimulatory molecule, and cytokine secretion via interacting with DCs [ 184 ]. These vaccines that have been preliminarily proven effective in animal experiments include a tumor-derived autophagome (Dribble) vaccine conjugated with mycobacterial HSP70407–426 (M2) peptide, soluble form of B, and T lymphocyte attenuator (sBTLA) in combination with HSP70 vaccine where recombinant adeno-associated viral (AAV) vectors served as the gene delivery, DCs pulsed with recombinant fusion protein of CEA 576–669 and HSP70-like protein 1 (HSP70L1), and DCs pulsed with tumor cell lysate which was pulsed with M2 peptide and OK-432 [ 185 , 186 , 187 , 188 , 189 ].…”

Section: Targeting Hsp70 In Cancer Therapymentioning

confidence: 99%

HSP70 Family in Cancer: Signaling Mechanisms and Therapeutic Advances

et al. 2023

View full text Add to dashboard Cite

The 70 kDa heat shock proteins (HSP70s) are a group of highly conserved and inducible heat shock proteins. One of the main functions of HSP70s is to act as molecular chaperones that are involved in a large variety of cellular protein folding and remodeling processes. HSP70s are found to be over-expressed and may serve as prognostic markers in many types of cancers. HSP70s are also involved in most of the molecular processes of cancer hallmarks as well as the growth and survival of cancer cells. In fact, many effects of HSP70s on cancer cells are not only related to their chaperone activities but rather to their roles in regulating cancer cell signaling. Therefore, a number of drugs directly or indirectly targeting HSP70s, and their co-chaperones have been developed aiming to treat cancer. In this review, we summarized HSP70-related cancer signaling pathways and corresponding key proteins regulated by the family of HSP70s and partner chaperons. In addition, we also summarized various treatment approaches and progress of anti-tumor therapy based on targeting HSP70 family proteins.

show abstract

Microbial HSP70 peptide epitope 407–426 as adjuvant in tumor-derived autophagosome vaccine therapy of mouse lung cancer

Cited by 10 publications

References 24 publications

Impact of a Heat Shock Protein Impurity on the Immunogenicity of Biotherapeutic Monoclonal Antibodies

Impact of a Heat Shock Protein Impurity on the Immunogenicity of Biotherapeutic Monoclonal Antibodies

Diversity of extracellular HSP70 in cancer: advancing from a molecular biomarker to a novel therapeutic target

HSP70 Family in Cancer: Signaling Mechanisms and Therapeutic Advances

Contact Info

Product

Resources

About