Tuberculosis vaccine developments and efficient delivery systems: A comprehensive appraisal.

Despite the widespread use of the Bacillus Calmette-Guérin (BCG) vaccine, Mycobacterium tuberculosis (MTB) continues to be a global burden. Vaccination has been proposed to prevent and treat tuberculosis (TB) infection, and several of them are in different phases of clinical trials. Though vaccine production is in progress but requires more attention. There are several TB vaccines in the trial phase, most of which are based on a combination of proteins/adjuvants or recombinant viral vectors used for selected MTB antigens. In this review, we attempted to discuss different types of TB vaccines based on the vaccine composition, the immune responses generated, and their clinical trial phases. Furthermore, we have briefly overviewed the effective delivery systems used for the TB vaccine and their effectiveness in different vaccines.

Development and characterization of phage display-derived anti-toxin antibodies neutralizing TcdA and TcdB of Clostridioides difficile.

TcdA and TcdB are known as the major virulence attributes of Clostridioides difficile. Hence, neutralizing the TcdA and TcdB activities can be considered as an efficient therapeutic approach against C. difficile infection (CDI). In this work, we utilized phage display technique to select single-chain fragment variable (scFv) fragments as recombinant antibodies displayed on the surface of phages, which specifically target native TcdA, or TcdB (nTcdA and nTcdB), and their recombinant C-terminal combined repetitive oligopeptide (CROP) domains (rTcdA and rTcdB). After three rounds of biopanning, abundance of phage clones displaying high reactivity with TcdA or TcdB was quantified through enzyme-linked immunosorbent assay (ELISA). Furthermore, selected scFvs were characterized by cell viability and neutralization assays. The gene expression of immunological markers, IL-8 and TNF-α, was examined in treated Caco-2 cells by RT-qPCR. The epitopes of neutralizing scFvs were also identified by molecular docking. Totally, 18 scFv antibodies (seven for TcdA and 11 for TcdB) were identified by ELISA. Among selected scFvs, two clones for TcdA (rA-C2, A-C9) and three clones for TcdB (rB-B4, B-F5, B-F11) exhibited the highest neutralizing activity in Caco-2 and Vero cells. Moreover, the cocktail of anti-TcdA and anti-TcdB antibodies notably decreased the mRNA expression of TNF-α and IL-8 in Caco-2 cells. Molecular docking revealed that the interaction between scFv and toxin was mostly restricted to CROP domain of TcdA or TcdB. Our results collectively provided more insights for the development of neutralizing scFvs against C. difficile toxins using phage display. Further research is needed to meticulously evaluate the potential of scFvs as an alternative treatment for CDI using animal models and clinical trials.IMPORTANCETargeting the major toxins of Clostridioides difficile by neutralizing antibodies is a novel therapeutic approach for CDI. Here, we report a panel of new anti-TcdA (rA-C2, A-C9) and anti-TcdB (rB-B4, B-F5, and B-F11) recombinant antibody fragments (scFvs) isolated from Tomlinson I and J libraries using phage display technique. These scFv antibodies were capable of neutralizing their respective toxin and showed promise as potential therapeutics against TcdA and TcdB of C. difficile in different in vitro models. In addition, in silico analysis showed that at least two neutralization mechanisms, including inhibiting cell surface binding of toxins and inhibiting toxin internalization can be proposed for the isolated scFvs in this work. These findings provide more insights for the applicability of specific scFvs toward C. difficile toxins at in vitro level. However, further research is required to evaluate the potential application of these scFvs as therapeutic agents for CDI treatment in clinical setting.

Chitosan nanoparticles containing fusion protein (Hspx-PPE44-EsxV) and resiquimod adjuvant (HPERC) as a novel booster vaccine for Mycobacterium tuberculosis.

This study attempted to explore the immunogenicity of chitosan nanoparticles containing fusion protein (Hspx-PPE44-EsxV; HPE) and resiquimod adjuvant (HPERC) in BALB/c mice. HPE was initially expressed in E. coli BL21 cells. HPE and resiquimod adjuvant were then encapsulated in chitosan nanoparticles (HPERC). One group of mice were subcutaneously vaccinated on days 0, 14, and 28 with HPERC, and the other group was primed with bacilli Calmette-Guérin (BCG) on day 0 and then boosted with HPERC on days 14 and 28. Two weeks after the last injection, IFN-γ, IL-4, and IL-17 in spleen cell culture supernatants, and IgG2a and IgG1 titers in sera were measured. HPERC size was 130.84 ± 12.08 nm (n = 5). Zeta potential of HPERC was 29 ± 4 mv. The highest IFN-γ concentration was detected in BCG-primed mice that were boosted with HPERC. In addition, IL-17 production was significantly increased in all groups compared with that of control, except in those that received nanoparticle (NP), adjuvant (ADJ), NP/ADJ, and fusion protein (Hspx-PPE44-EsxV) (HPE). Comparison of IFN-γ and IL-4 concentration determined that Th1 was activated in BCG-primed and HPERC-boosted group in comparison to the other groups. No significant difference in concentration of IL-4 was observed between groups receiving HPERC and BCG-primed and HPERC-boosted group in comparison to group BCG. Concentrations of IgG2a and IgG1 also increased compared to the control group and the rate of IgG2a was higher compared to IgG1. Chitosan containing HPERC vaccine could induce a high level of specific cytokines in mice. The group of mice which first received BCG and then HPERC as booster vaccine could produce significant amounts of IFN-γ, IL-17, and IgG2a.

Nanoencapsulation of Hirudo medicinalis proteins in liposomes as a nanocarrier for inhibiting angiogenesis through targeting VEGFA in the Breast cancer cell line (MCF-7).

Introduction: Breast cancer is the most serious cause of women's death throughout the world. Using nanocarrier vehicles to the exact site of cancer upgrades the therapeutic efficiency of the drugs. Capsulation of active proteins in the vesicular liposomes' hydrophilic core is essential to develop a therapeutic protein carrier system. We aimed to encapsulate the medicinal leech saliva extract (LSE) and assess the inhibition of angiogenesis of breast cancer cells by targeting vascular endothelial growth factor A (VEGFA). Methods: In this research, enhanced formulation of liposomal protein was determined by zeta potential analysis, droplet size, drug release assay, and transmission electron microscopy (TEM). Furthermore, a cytotoxicity assay of liposomal LSE was performed to determine the cytotoxic activity of components. For assessing the expression of VEGFA, P53, and hypoxia-inducible factor subunit alpha (HIF1a) genes, Real-Time PCR was applied. Results: Nano liposome was chosen as an enhanced formulation due to its much smaller size (46.23 nm). Liposomal LSE had more practical actions on the MCF-7 cells. As noticed by DAPI staining, apoptosis was extensively greater in treated MCF-7 cells. Wound healing assay demonstrated that MCF-7 cells could not sustain growth at the presence of liposomal LSE and expression of the VEGFA gene was declined in treated cells. Downregulation of VEGFA was evaluated with western blotting technique. Conclusion: It can be concluded that our investigation of the tests confirmed the fact that nano liposomal LSE is a novel promising formulation for anticancer drugs and can significantly improve the penetration of protein drugs to cancer cells.

Cancer stem cell-targeted chimeric antigen receptor (CAR)-T cell therapy: Challenges and prospects.

Cancer stem cells (CSCs) with their self-renewal ability are accepted as cells which initiate tumors. CSCs are regarded as interesting targets for novel anticancer therapeutic agents because of their association with tumor recurrence and resistance to conventional therapies, including radiotherapy and chemotherapy. Chimeric antigen receptor (CAR)-T cells are engineered T cells which express an artificial receptor specific for tumor associated antigens (TAAs) by which they accurately target and kill cancer cells. In recent years, CAR-T cell therapy has shown more efficiency in cancer treatment, particularly regarding blood cancers. The expression of specific markers such as TAAs on CSCs in varied cancer types makes them as potent tools for CAR-T cell therapy. Here we review the CSC markers that have been previously targeted with CAR-T cells, as well as the CSC markers that may be used as possible targets for CAR-T cell therapy in the future. Furthermore, we will detail the most important obstacles against CAR-T cell therapy and suggest solutions.

Recent advances in the application of probiotic yeasts, particularly Saccharomyces, as an adjuvant therapy in the management of cancer with focus on colorectal cancer.

Today, the increasing rate of cancer-related mortality, has rendered cancer a major global challenge, and the second leading cause of death worldwide. Conventional approaches in the treatment of cancer mainly include chemotherapy, surgery, immunotherapy, and radiotherapy. However, these approaches still come with certain disadvantages, including drug resistance, and different side effects such as gastrointestinal (GI) irritation (e.g., diarrhea, mucositis). This has encouraged scientists to look for alternative therapeutic methods and adjuvant therapies for a more proper treatment of malignancies. Application of probiotics as an adjuvant therapy in the clinical management of cancer appears to be a promising strategy, with several notable advantages, e.g., increased safety, higher tolerance, and negligible GI side effects. Both in vivo and in vitro analyses have indicated the active role of yeast probiotics in mitigating the rate of cancer cell proliferation, and the induction of apoptosis through regulating the expression of cancer-related genes and cellular pathways. Strain-specific anti-cancer activities of yeast probiotics strongly suggest that their administration along with the current cancer therapies may be an efficient method to reduce the side effects of these approaches. The main purpose of this article is to evaluate the efficacy of yeast probiotics in alleviating the adverse effects associated with cancer therapies.

Hsp70 in cancer: A double agent in the battle between survival and death.

The heat shock protein (Hsps) superfamily, also known as molecular chaperones, are highly conserved and present in all living organisms and play vital roles in protein fate. The HspA1A (Hsp70-1), called Hsp70 in this review, is expressed at low or undetectable levels in most unstressed normal cells, but numerous studies have shown that diverse types of tumor cells express Hsp70 at the plasma membrane that leads to resistance to programmed cell death and tumor progression. Hsp70 is released into the extracellular milieu in three forms including free soluble, complexed with cancer antigenic peptides, and exosome forms. Therefore, it seems to be a promising therapeutic target in human malignancies. However, a great number of studies have indicated that both intracellular and extracellular Hsp70 have a dual function. A line of evidence presented that intracellular Hsp70 has a cytoprotective function via suppression of apoptosis and lysosomal cell death (LCD) as well as that extracellular Hsp70 can promote tumorigenesis and angiogenesis. Other evidence showed intracellular Hsp70 can promote apoptosis and membrane-associated/extracellular Hsp70 can elicit antitumor innate and adaptive immune responses. Given the contradictory functions, as a "double agent," could Hsp70 be a promising tool in the future of targeted cancer therapies? To answer this question, in this review, we will discuss the functions of Hsp70 in cancers besides inhibition and stimulation strategies for targeting Hsp70 along with their challenges.

PCSK9: A Key Target for the Treatment of Cardiovascular Disease (CVD).

Proprotein convertase subtilisin/kexin type 9 (PCSK9), as a vital modulator of low-density lipoprotein cholesterol (LDL-C) , is raised in hepatocytes and released into plasma where it binds to LDL receptors (LDLR), leading to their cleavage. PCSK9 adheres to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR which is confirmed by crystallography. LDLR expression is adjusted at the transcriptional level through sterol regulatory element binding protein 2 (SREBP-2) and at the post translational stages, specifically through PCSK9, and the inducible degrader of the LDLR PCSK9 inhibition is an appealing new method for reducing the concentration of LDL-C. In this review the role of PCSK9 in lipid homeostasis was elucidated, the effect of PCSK9 on atherosclerosis was highlighted, and contemporary therapeutic techniques that focused on PCSK9 were summarized. Several restoration methods to inhibit PCSK9 have been proposed which concentrate on both extracellular and intracellular PCSK9, and they include blockage of PCSK9 production by using gene silencing agents and blockage of it's binding to LDLR through antibodies and inhibition of PCSK9 autocatalytic processes by tiny molecule inhibitors.

Tumor-Associated Macrophages: Protumoral Macrophages in Inflammatory Tumor Microenvironment.

Tumor microenvironment consists of malignant and non-malignant cells. The interaction of these dynamic and different cells is responsible for tumor progression at different levels. The non-malignant cells in TME contain cells such as tumor-associated macrophages (TAMs), cancer associated fibroblasts, pericytes, adipocytes, T cells, B cells, myeloid-derived suppressor cells (MDSCs), tumor-associated neutrophils (TANs), dendritic cells (DCs) and Vascular endothelial cells. TAMs are abundant in most human and murine cancers and their presence are associated with poor prognosis. The major event in tumor microenvironment is macrophage polarization into tumor-suppressive M1 or tumor-promoting M2 types. Although much evidence suggests that TAMS are primarily M2-like macrophages, the mechanism responsible for polarization into M1 and M2 macrophages remain unclear. TAM contributes cancer cell motility, invasion, metastases and angiogenesis. The relationship between TAM and tumor cells lead to used them as a diagnostic marker, therapeutic target and prognosis of cancer. This review presents the origin, polarization, role of TAMs in inflammation, metastasis, immune evasion and angiogenesis as well as they can be used as therapeutic target in variety of cancer cells. It is obvious that additional substantial and preclinical research is needed to support the effectiveness and applicability of this new and promising strategy for cancer treatment.

Production and purification of polyclonal antibody against attenuated and wild type Leishmania infantum in dogs.

Antibodies are still widely used in several programs including early research, imaging, Targeting drug delivery system, Affinity chromatography, flowcytometry technic, diagnosis and treatment. Purification of antibody is a standard approach for detection of infection agent in different species. The reservoir hosts for Leishmania infantum are Dogs and they have active role in the transmission of leishmania to humans by the bite of a sand fly belonging to genus Phlebotomus and Lutzomiya. Consequently, elimination of dogs in endemic areas and vaccination of dogs contributes to reduction of the human and canine VL cases. Serological antibody tests such as IFAT (Indirect Fluorescent Antbody Test), DFAT (Direct Fluorescent Antbody Test), ELISA (Enzyme-Linked Immunosorbent Assay), PCR (Polymerase chain Reaction Assay) have been extensively used to investigate canine infection with L. infantum. In this study we produced and purified polyclonal antibody against attenuated and wild type leishmania infantum in dogs. Anti-leishmania in dog serums precipitated with ammonium sulphate. The IgG recovered from ammonium sulphate precipitation was subject to ion exchange chromatography (IEC) and the purity of IgG was confirmed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) under reduced condition. The purity of proteins were above 95% and then purified IgG was conjugated with FITC. We determined optimum titer of dog IgG by observation parasites under fluorescent microscope. The optimum dilution of prepared FITC conjugated dog IgG was 1: 400. This polyclonal antibody can be used for other applications in research, diagnosis and clinic.

Role of Apelin/APJ axis in cancer development and progression.

Apelin is an endogenous peptide, which is expressed in a vast board of organs such as the brain, placenta, heart, lungs, kidneys, pancreas, testis, prostate and adipose tissues. The apelin receptor, called angiotensin-like-receptor 1 (APJ), is also expressed in the brain, spleen, placenta, heart, liver, intestine, prostate, thymus, testis, ovary, lungs, kidneys, stomach, and adipose tissue. The apelin/APJ axis is involved in a number of physiological and pathological processes. The apelin expression is increased in various kinds of cancer and the apelin/APJ axis plays a key role in the development of tumors through enhancing angiogenesis, metastasis, cell proliferation and also through the development of cancer stem cells and drug resistance. The apelin also stops the apoptosis of cancer cells. The apelin/APJ axis was considered in this review as an attractive therapeutic target for cancer treatment.

Apoptotic Effect of Saccharomyces cerevisiae on Human Colon Cancer SW480 Cells by Regulation of Akt/NF-ĸB Signaling Pathway.

Drug resistance is one of the major problems, which causes recurrence of cancers. Therefore, complementary treatments are needed to improve the impacts of chemotherapy agents. The effect of probiotics as cancer-preventing agents through involvement in the activation of apoptotic pathways has been established. The present study sought to investigate how the heat-killed form of Saccharomyces cerevisiae (as a probiotic) could affect the Akt/NF-kB-induced apoptosis in colon cancer cells, the SW480 cell line. The cytotoxic effects of heat-killed yeast (HKY) and 5-fluorouracil (5-FU, as a positive control drug) were assayed using the MTT method. Morphological changes followed by apoptosis were examined using DAPI staining. The transcription and translation level of apoptosis genes were explored with qRT-PCR and western blotting. The data were analyzed using GraphPad Prism V6.0 Software. The results showed that HKY could induce apoptosis in colon cancer cell line through downregulation of p-Akt1, Rel A, Bcl-XL, pro-caspase 3, and pro-caspase 9 expressions, and upregulation of BAX, cleaved caspase-3, and cleaved caspase-9. Besides, Akt protein expression was not affected. It is noticeable that HKY had a better modulating effect on BAX expression compared with 5-FU. It was able to modulate Akt/NF-kB signaling pathway followed by the apoptotic cascade.

Purification of hyaluronidase as an anticancer agent inhibiting CD44.

Hyaluronidase (Hyal) can be employed to accomplish a diversity of complications related to hyaluronic acid (HA). Hyal contains some classes of catalysts that cleave HA. This enzyme is detected in several human tissues as well as in animal venoms, pathogenic organisms and cancers. Destructive cancer cells regularly increase the CD44 receptor existing in a cell membrane. This receptor acts as an exact receptor for HA, and HA is recognized to motivate the migration, spread, attack and metastasis of cancer cells. Nearly all of the methods used to purify Hyal are highly costly and not proper for industrial applications. This survey aims to review different methods of Hyal purification, which acts as an anticancer agent by degrading HA in tissues and thus inhibiting the CD44-HA interaction. Hyal can be successfully employed in the management of cancer, which is associated with HA-CD44. This review has described different methods for Hyal purification to prepare an origin to develop a novel purification technique for this highly appreciated protein. Using multiple columns is not applicable for the purification of Hyal and thus cannot be used at the industrial level. It is better to use affinity chromatography of anti-Hyal for Hyal with one-step purification.

Development and characterization of polyclonal antibody against human kappa light chain in rabbit.

Polyclonal antibodies against kappa light chain are used to diagnose diseases producing free light chain. The kappa and lambda light chains are products of immunoglobulin synthesis and released into the circulation in minor amounts such as serum, cerebrospinal fluid, urine and synovial fluid in normal condition. The purpose of this study was the production and purification of polyclonal immunoglobulin G (IgG) against human kappa light chains. In this study, early human IgG was purified by ion-exchange chromatography, reduced with Dithiothreitol and heavy and light chains were separated with size-exclusion chromatography. Afterward, affinity chromatography with protein L Sepharose at pH 2.00 was displayed to be a dominant condition for the separation and purification of the kappa light chain of immunoglobulins from human serum. Eventually, the rabbit was immunized by human kappa light chains. The rabbit IgG was purified and labeled with horseradish peroxidase (HRP). Direct enzyme-linked immunosorbent assay was planned to determine the titer of HRP conjugated rabbit IgG against the human kappa light chain. The optimum titer of anti-kappa IgG was 1:16000. At the result, purified polyclonal anti-kappa is useful tool in biomedical and biochemical researches and diagnostic kits.

Isolation of a Novel Anti-KDR3 Single-chain Variable Fragment Antibody from a Phage Display Library.

Vascular endothelial growth factor receptor 2 (VEGFR-2) is known as one of the important antigens playing a vital role in angiogenesis. In this study, phage display technology (PDT) was used to produce a single-chain variable fragment (scFv) antibody against a region of the domain 3 in VEGFR-2 called kinase insert domain receptor 3 (KDR3). After designing the KDR3 peptide and biopanning, a colony was chosen for scFv antibody expression. Following expression and purification; western blotting, dot blotting and immunofluorescence (IF) were used to evaluate the antibody function. Surface plasmon resonance (SPR) was also employed to measure affinity of produced antibody. Once a colony was selected and transferred to the expression host, the scFv antibody was expressed in the expected range of 28 kDa. Using a designed chromatography column, antibody purification was found to be about 95%. In this study, a novel scFv with the capability of binding to KDR3 was isolated and purified and its intracellular function was investigated and verified.

Correction to: Modulation of lipolysis and glycolysis pathways in cancer stem cells changed multipotentiality and differentiation capacity toward endothelial lineage.

[This corrects the article DOI: 10.1186/s13578-019-0293-z.].

Modulation of lipolysis and glycolysis pathways in cancer stem cells changed multipotentiality and differentiation capacity toward endothelial lineage.

Cancer stem cells obtain energy demand through the activation of glycolysis and lipolysis. It seems that the use of approached targeting glycolysis and lipolysis could be an effective strategy for the inhibition of cancer stem cells. In the current experiment, we studied the potential effect of glycolysis and lipolysis inhibition on cancer stem cells differentiation and mesenchymal-epithelial-transition capacity. Cancer stem cells were enriched from human ovarian cells namely SKOV3 by using MACS technique. Cells were exposed to Lonidamine, an inhibitor of glycolysis, and TOFA, a potent inhibitor of lipolysis for 7 days in endothelial differentiation medium; EGM-2 and cell viability was studied by MTT assay. At the respective time point, the transcription level of genes participating in EMT such as Zeb-1, -2, Vimentin, Snail-1, -2 and VE-cadherin were measured by real-time PCR analysis. Our data noted that the inhibition of lipolysis and glycolysis could decrease cell viability compared to the control of cancer stem cells. The inhibition of glycolysis prohibited the expression of Zeb-1, Snails, and Vimentin while increased endothelial differentiation rate indicated by the expression of VE-cadherin. In contrast, the inhibition of lipolysis increased EMT associated genes and reduced endothelial differentiation rate by suppressing the transcription of VE-cadherin. Notably, the simultaneous inhibition of glycolysis and lipolysis had moderate effects on the transcription of EMT genes. We concluded that the modulation of the metabolic pathway of glycolysis in ovarian CSCs is more effective than the inhibition of lipolysis in the control of angiogenesis potential and stemness feature.

Isolation and characterization of a novel scFv antibody fragments specific for Hsp70 as a tumor biomarker.

Many studies have shown that more than 50% of tumors express heat shock protein 70 kDa (Hsp70) at the plasma membrane surface while not seen in normal cells, therefore it is a promising therapeutic target in human cancers. Hence, we used phage display technology to produce a single-chain fragment variable (scFv) antibody against human Hsp70. For this, a target peptide from human Hsp70 was designed using bioinformatics studies and was chemically synthesized. Then, the selection was performed using four rounds of biopanning with a stepwise decreased amount of the target peptide. Fourteen positive scFv clones were selected using monoclonal phage enzyme-linked immunosorbent assay screening, which was further characterized by means of the polymerase chain reaction and DNA sequencing. Among them, the G6 clone was selected to express scFv into the Escherichia coli. Expression and purification of the scFv shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and confirmed by Western blot analysis. In silico analysis confirmed specific binding of the scFv to Hsp70 in CDR regions. The specificity of the scFv measured by surface plasmon resonance and immunofluorescence of the A549 human lung carcinoma cell line confirmed the in vitro function of the scFv. Based upon these findings, we propose a novel anti-human Hsp70 scFv as potential immunotherapy agents that may be translated into preclinical/clinical applications.

Purification of a Novel Anti-VEGFR2 Single Chain Antibody Fragment and Evaluation of Binding Affinity by Surface Plasmon Resonance.

Purpose: The single-chain variable fragment (scFv) domain of antibodies is now considered as one of the therapeutic tools that can be produced by phage display technology (PDT). Antibody purification is one of the most important steps in antibodies production. The aim of study was purification and characterization of anti-VEGFR2 scFv antibody fragments. Methods: After the coating of vascular endothelial growth factor receptor 2 (VEGFR2) peptide in ELISA microplates, the phage display library of Tomlinson was used for antibody isolation. The targeted scFv was purified by chromatography using a zeolite-based column. The purity and functional assessment of purified scFv were evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting techniques, respectively. Affinity binding was evaluated by surface plasmon resonance (SPR). Results: The desired scFv was selected after four stages of biopanning. SDS-PAGE analysis showed a 28 kDa scFv with high purity (>90%). The western bloting analysis confirmed the binding of produced scFv antibody to the desired peptide. The affinity binding of scFv antibody analyzed by SPR was about 60 µM. Conclusion: In this study, the novel scFv antibody against VEGFR2 peptide was purified by chromatography column containing zeolite. Based on our findings the produced antibody may be applied for diagnosis or targeting of VEGFR2 in antibody-based therapy strategies.

Hsp70 in Cancer: Partner or Traitor to Immune System.

Heat shock protein 70.1 (Hsp70.1), also known as Hsp70, is a highly conserved member of the heat shock protein family that exists in all living organisms and determines the protein fate as molecular chaperones. Hsp70 basal expression is undetectable or low in most unstressed normal cells, however, its abundant presence in several types of human cancer cells is reported. Several studies support upregulated Hsp70 involved in tumor progression and drug resistance through modulation of cell death pathways and suppresses anticancer immune responses. However, numerous studies have confirmed that Hsp70 can also induce anticancer immune responses through the activation of immune cells in particular antigen-presenting cells (APCs). Regarding the significant and the promising role of vaccines in cancer immunotherapy, identification and characterization of the overexpressed Hsp70 as a potential immune stimulatory factor can pave the path for development of highly effective anticancer vaccines. In this review, we will discuss the interactions of Hsp70 with components of the immune system in cancers as well as possible strategies to harness Hsp70 for eliciting anticancer immune responses.