Source Of Antigen Research Articles

Reactivity of purified and axenic amastigotes as a source of antigens to be used in serodiagnosis of canine visceral leishmaniasis.

Although there is a great diversity of techniques and antigens used in the serodiagnosis of canine visceral leishmaniasis (CVL), total sensitivity and specificity have not yet been found. Since the use of amastigote forms in the indirect immunofluorescence assay has shown an improvement in the specificity of the test for the diagnosis of CVL, the performance of amastigotes forms of L. (L.) infantum chagasi as antigen source were evaluated in automatized ELISA test using crude antigen of axenic amastigote and purified amastigote from spleen of hamster chronically infected comparing with ELISA using total antigen produced with promastigote forms of L. (L.) infantum chagasi. One hundred and fifteen sera from dogs with positive parasitological diagnosis by PCR were used. The animals were classified into 2 groups: symptomatic (n=67) and asymptomatic (n=48) animals, in accordance with the clinical signs and laboratory tests were. As control, ninety-four sera from dogs with negative parasitological diagnosis were included. No significant difference was found in sensitivity, specificity, predictive values and accuracy between ELISA using whole antigens produced with both axenic and purified amastigotes in comparison with promastigotes forms. Correlation and concordance between the three total antigens tested in ELISA was observed. According to the similar performance among antigens, data pointed out to use antigen from promastigote forms for diagnosing canine leishmaniasis, especially due the easily in the production, lower cost and the abundance of correlative literature.

Plasma Tau Variants Detected by a Novel Anti-Tau Monoclonal Antibody: A Potential Biomarker for Alzheimer's Disease.

A major drawback in Alzheimer's disease (AD) is the lack of validated biomarkers for routine clinical diagnostic. We have reported earlier a novel blood biomarker, named Alz-tau®, based on variants of platelet tau. This marker evaluates the ratio of high molecular weight tau (HMWtau) and the low molecular weight (LMWtau) tau. To analyze a potential novel source of antigen for Alz-tau®, plasma tau, detected by immunoreactivity with the novel monoclonal antibody, tau51. We evaluated tau variants in plasma precipitated with ammonium sulfate from 36 AD patients and 15 control subjects by western blot with this novel monoclonal antibody. The HMW/LMWtau ratio was statistically different between AD patients and controls. Plasma tau variants are suitable to be considered as a novel antigen source for the Alz-tau® biomarker for AD.

Protective effect of fungal extracellular vesicles against murine candidiasis.

Extracellular vesicles (EVs) are lipid bilayered compartments released by virtually all living cells, including fungi. Among the diverse molecules carried by fungal EVs, a number of immunogens, virulence factors and regulators have been characterised. Within EVs, these components could potentially impact disease outcomes by interacting with the host. From this perspective, we previously demonstrated that EVs from Candida albicans could be taken up by and activate macrophages and dendritic cells to produce cytokines and express costimulatory molecules. Moreover, pre-treatment of Galleria mellonella larvae with fungal EVs protected the insects against a subsequent lethal infection with C. albicans yeasts. These data indicate that C. albicans EVs are multi-antigenic compartments that activate the innate immune system and could be exploited as vaccine formulations. Here, we investigated whether immunisation with C. albicans EVs induces a protective effect against murine candidiasis in immunosuppressed mice. Total and fungal antigen-specific serum IgG antibodies increased by 21 days after immunisation, confirming the efficacy of the protocol. Vaccination decreased fungal burden in the liver, spleen and kidney of mice challenged with C. albicans. Splenic levels of cytokines indicated a lower inflammatory response in mice immunised with EVs when compared with EVs + Freund's adjuvant (ADJ). Higher levels of IL-12p70, TNFα and IFNγ were detected in mice vaccinated with EVs + ADJ, while IL-12p70, TGFβ, IL-4 and IL-10 were increased when no adjuvants were added. Full protection of lethally challenged mice was observed when EVs were administered, regardless the presence of adjuvant. Physical properties of the EVs were also investigated and EVs produced by C. albicans were relatively stable after storage at 4, -20 or -80°C, keeping their ability to activate dendritic cells and to protect G. mellonella against a lethal candidiasis. Our data suggest that fungal EVs could be a safe source of antigens to be exploited in vaccine formulations.

HIV-2-Infected Macrophages Produce and Accumulate Poorly Infectious Viral Particles.

A significant proportion of HIV-2-infected patients exhibit natural virological control that is generally absent from HIV-1-infected patients. Along with CD4+ T cells, HIV-1 targets macrophages which may contribute to viral spreading and the latent reservoir. We have studied the relationship between macrophages and HIV-2, focusing on post-entry steps. HIV-2-infected monocyte-derived macrophages (MDMs) produced substantial amounts of viral particles that were largely harbored intracellularly. New viruses assembled at the limiting membrane of internal compartments similar to virus-containing compartments (VCCs) described for HIV-1. VCCs from MDMs infected with either virus shared protein composition and morphology. Strikingly, HIV-2 Gag was mostly absent from the cytosol and almost exclusively localized to the VCCs, whereas HIV-1 Gag was distributed in both locations. Ultrastructural analyses of HIV-2-infected MDMs revealed the presence of numerous VCCs containing both immature and mature particles in the lumen. HIV-2 particles produced de novo by MDMs were poorly infectious in reporter cells and in transmission to activated T cells through a process that appeared independent of BST2 restriction. Rather than being involved in viral spreading, HIV-2-infected macrophages may represent a cell-associated source of viral antigens that can participate in the immune control of HIV-2 infection.

Characterization of the antiviral effects of REP 2139 on the HBV lifecycle in vitro

During hepatitis B virus (HBV) infection, HBV subviral particles (SVP) are produced in large excess in comparison to infectious virions and account for the major source of HBV surface antigen (HBsAg) in the blood. This abundant circulating HBsAg has been postulated to promote HBV chronicity by inducing immune exhaustion against HBsAg. Nucleic acid polymers (NAPs) such as REP 2139 display promising antiviral activity against both HBV and hepatitis Delta virus (HDV) in clinical trials. REP 2139 is accompanied by clearance of HBsAg from blood with concomitant reappearance of anti-HBsAg antibodies. To decipher the mechanism-of-action of NAPs, a recently developed cell-based assay in human HepG2.2.15 cells was used (Blanchet et al., 2019). This assay recapitulates the HBsAg secretion inhibition observed in treated patients. In the present study, we analysed the antiviral effect of REP 2139 on the HBV lifecycle. Importantly, we confirm here the potent inhibitory activity of the compound on HBsAg secretion, and report minor or no effect on other viral markers such as intracellular DNA and RNA, and HBeAg or Dane particle secretion. Notably, intracellular HBsAg accumulation is prevented by proteasomal and lysosomal degradation.

Search of Potential Vaccine Candidates against Trueperella pyogenes Infections through Proteomic and Bioinformatic Analysis.

Trueperella pyogenes is an opportunistic pathogen, responsible for important infections in pigs and significant economic losses in swine production. To date, there are no available commercial vaccines to control diseases caused by this bacterium. In this work, we performed a comparative proteomic analysis of 15 T. pyogenes clinical isolates, by “shaving” live cells, followed by LC-MS/MS, aiming at the identification of the whole set of surface proteins (i.e., the “pan-surfome”) as a source of antigens to be tested in further studies as putative vaccine candidates, or used in diagnostic tools. A total of 140 surface proteins were detected, comprising 25 cell wall proteins, 10 secreted proteins, 23 lipoproteins and 82 membrane proteins. After describing the “pan-surfome”, the identified proteins were ranked in three different groups based on the following criteria: to be (i) surface-exposed, (ii) highly conserved and (iii) widely distributed among different isolates. Two cell wall proteins, three lipoproteins, four secreted and seven membrane proteins were identified in more than 70% of the studied strains, were highly expressed and highly conserved. These proteins are potential candidates, alone or in combination, to obtain effective vaccines against T. pyogenes or to be used in the diagnosis of this pathogen.

Deciphering the Mechanisms of Improved Immunogenicity of Hypochlorous Acid-Treated Antigens in Anti-Cancer Dendritic Cell-Based Vaccines.

Hypochlorous acid (HOCl)-treated whole tumor cell lysates (Ox-L) have been shown to be more immunogenic when used as an antigen source for therapeutic dendritic cell (DC)-based vaccines, improving downstream immune responses both in vitro and in vivo. However, the mechanisms behind the improved immunogenicity are still elusive. To address this question, we conducted a proteomic and immunopeptidomics analyses to map modifications and alterations introduced by HOCl treatment using a human melanoma cell line as a model system. First, we show that one-hour HOCl incubation readily induces extensive protein oxidation, mitochondrial biogenesis, and increased expression of chaperones and antioxidant proteins, all features indicative of an activation of oxidative stress-response pathways. Characterization of the DC proteome after loading with HOCl treated tumor lysate (Ox-L) showed no significant difference compared to loading with untreated whole tumor lysate (FT-L). On the other hand, detailed immunopeptidomic analyses on monocyte-derived DCs (mo-DCs) revealed a great increase in human leukocyte antigen class II (HLA-II) presentation in mo-DCs loaded with Ox-L compared to the FT-L control. Further, 2026 HLA-II ligands uniquely presented on Ox-L-loaded mo-DCs were identified. In comparison, identities and intensities of HLA class I (HLA-I) ligands were overall comparable. We found that HLA-II ligands uniquely presented by DCs loaded with Ox-L were more solvent exposed in the structures of their source proteins, contrary to what has been hypothesized so far. Analyses from a phase I clinical trial showed that vaccinating patients using autologous Ox-L as an antigen source efficiently induces polyfunctional vaccine-specific CD4+ T cell responses. Hence, these results suggest that the increased immunogenicity of Ox-L is, at least in part, due to qualitative and quantitative changes in the HLA-II ligandome, potentially leading to an increased HLA-II dependent stimulation of the T cell compartment (i.e., CD4+ T cell responses). These results further contribute to the development of more effective and immunogenic DC-based vaccines and to the molecular understanding of the mechanism behind HOCl adjuvant properties.

Future directions of neoadjuvant therapy in pancreatic cancer.

Neoadjuvant therapy with conventional chemotherapies have visibly improved the prognosis of locally advanced pancreatic cancer (PCa). However, molecular targeted therapies that have provided durable responses in other tumor entities, have not yet found access into neoadjuvant therapy of PCa. In fact, due to the presence of the tumor burden serving as an antigen source for T cell priming, neoadjuvant chemotherapy may unleash a more potent antitumoral immune response than adjuvant or palliative chemotherapy.

Development of a Multiplex Bead Serological Assay for Use in Global Laboratories to Assess Population Immunity to Measles and Rubella

Abstract Serosurveys are an important tool for the evaluation of population immunity and guidance of immunization activities. The multiplex bead assay (MBA) offers multiple benefits over standard serological assays and this study sought to compare the use of MBA to measure humoral immunity to measles and rubella compared to the enzyme immunoassay (EIA) for both viruses and the plaque reduction neutralization (PRN) for measles. Multiplex beads coupled with laboratory-produced purified measles whole virus antigen (WVA) correlated better to EIA and PRN than baculovirus-expressed measles nucleoprotein (N); therefore, a commercial antigen source of measles WVA was evaluated. The commercial measles WVA demonstrated significant correlation using Pearson’s correlation coefficient to the laboratory-produced WVA MBA (R=0.995, p=<0.0001) and demonstrated a strong linear relationship between the two WVA MBA assays (R2= 0.926). The commercial measles WVA MBA correlated strongly to PRN (R=0.9530, p=<0.0001) with a linear relationship comparable to the laboratory-produced WVA and PRN (R2=0.716 and R2=0.768, respectively). Receiver operator curve (ROC) analysis resulted in a seroprotection cutoff of 153 mIU/ml, similar to the established correlate of protection of 120 mIU/ml, with a sensitivity of 98% and a specificity of 84%. Comparison of the rubella MBA to EIA demonstrated a strong linear correlation of the two assays (R=0.959 and R2=0.919). ROC analysis yielded a cutoff of 9.36 IU/ml, similar to the accepted cutoff of 10 IU/ml for seroprotection with a sensitivity of 99% and a specificity of 100%. The results presented here support the use of the MBA as a tool to conduct multiplexed serosurveys to assess population immunity to measles and rubella.

Appropriate Use Criteria for Imaging Evaluation of Biochemical Recurrence of Prostate Cancer After Definitive Primary Treatment.

Imaging is often used to evaluate men with biochemical recurrence (BCR) of prostate cancer after definitive primary treatment (radical prostatectomy [RP] or radiotherapy [RT]). The goal of imaging is to identify the source of elevated or rising serum prostate-specific antigen (PSA) levels because

Analysis of Systemic Transport Barriers for the Activation of Anti‐tumor Immunity

Initiation of an immune response requires activation of one or more naïve T cells. Each naïve T cell has a unique T cell receptor, and these cells traffic through the blood and lymphatic vasculatures, visiting each of the ~500 lymph nodes in search of matching antigen. If a match is made, then the naïve T cell activates and proliferates. The resulting effector T cells enter the blood circulation to find and eradicate the source of antigen. Similar to pathogens like viruses, tumors can also create antigen that accumulates in local lymph nodes, where it can activate T cells. Unfortunately, even when this happens and the anti‐cancer effector cells find the tumor, they are prevented from killing by immune checkpoint programs that quench the immune response. In the past few years, multiple drugs have been approved that block these checkpoint programs, re‐enabling anti‐tumor immunity, and there have been miraculous cures in a subset of patients. However, there is an urgent need to understand why most patients (~85%) do not respond to these therapies. We explore the hypothesis that immune activation in these non‐responding patients is prevented or delayed due to transport limitations caused by the tumor that prevent colocalization of cognate naïve T cells and tumor antigen in the same lymph node. The model provides a mechanistic framework for optimizing cancer immunotherapy and developing testable solutions to unleash anti‐tumor immune responses for more patients with cancer.

Beta cell-specific CD8+ T cells maintain stem cell memory-associated epigenetic programs during type 1 diabetes.

The pool of beta cell-specific CD8+ T-cells in type 1 diabetes (T1D) sustains an autoreactive potential despite having access to a constant source of antigen. To investigate the long-lived nature of these cells, we established a DNA methylation-based T cell “multipotency index” and found that beta cell-specific CD8+ T-cells retained a stem-like epigenetic multipotency score. Single cell ATAC-seq analysis confirmed the co-existence of naive and effector-associated epigenetic programs in individual beta cell-specific CD8+ T-cells. Assessment of beta cell-specific CD8+ T-cell anatomical distribution and the establishment of stem-associated epigenetic programs revealed that self-reactive CD8+ T-cells isolated from murine lymphoid tissue retained developmentally plastic phenotypic and epigenetic profiles relative to the same cells isolated from the pancreas. Collectively, these data provide new insight into the longevity of beta cell-specific CD8+ T cell responses, and document the utility of this novel methylation-based multipotency index for investigating human and mouse CD8+ T-cell differentiation.

Development of Tumor Cell-Based Vaccine with IL-12 Gene Electrotransfer as Adjuvant.

Tumor cell-based vaccines use tumor cells as a source of tumor-associated antigens. In our study, we aimed to develop and test a tumor vaccine composed of tumor cells killed by irradiation combined with in vivo interleukin-12 gene electrotransfer as an adjuvant. Vaccination was performed in the skin of B16-F10 malignant melanoma or CT26 colorectal carcinoma tumor-bearing mice, distant from the tumor site and combined with concurrent tumor irradiation. Vaccination was also performed before tumor inoculation in both tumor models and tumor outgrowth was followed. The antitumor efficacy of vaccination in combination with tumor irradiation or preventative vaccination varied between the tumor models. A synergistic effect between vaccination and irradiation was observed in the B16-F10, but not in the CT26 tumor model. In contrast, up to 56% of mice were protected from tumor outgrowth in the CT26 tumor model and none were protected in the B16-F10 tumor model. The results suggest a greater contribution of the therapeutic vaccination to tumor irradiation in a less immunogenic B16-F10 tumor model, in contrast to preventative vaccination, which has shown greater efficacy in a more immunogenic CT26 tumor model. Upon further optimization of the vaccination and irradiation regimen, our vaccine could present an alternative tumor cell-based vaccine.

29-kDa: A Potential Candidate for Anti-Tick Vaccine Antigen Source as Immunogenic and Stage Reactive Targeting Hard-Bodied Hyalomma Ticks Ixodidae

The objective of present study is to develop a vaccine against Hyalomma hard-bodied tick and to analyze relevant experimental data on immunized indigenous horse breed Morna. Montanide (ISA-50) adjuvant-based vaccine induced significantly (pandlt;0.02) higher antibody titre through intradermal route with 99.98% vaccine efficacy. Humoral response was determined though indirect ELISA; where peak level of serum antibody was recorded after six weeks interval of post-immunization. Most of hematology and biochemical parameters remained consistent to normal reference values. Our report also indicates a significant percentage decline in the numbers of engorged ticks, eggs mass, eggs number and increased tick rejection. The animal travel history can promote tick burden and is a potential risk factor. Based on biological and hematological parameters, it is possible to conclude that 29-kDa antigen can be used as an effective antigen vaccine candidate to control tick infestation detected through humoral response.

Fiber optic interferometric immunosensor based on polydimethilsiloxane (PDMS) and bioactive lipids.

We demonstrate a novel and simple means to fabricate optical fiber immunosensors based on Fabry-Perot (F-P) interferometers using polydimethylsiloxane (PDMS) as support for bioactive lipids. The sensors are fabricated following a straightforward dip-coating method producing PDMS end-capped devices. A biosensing platform is realized by subsequent functionalization of the PDMS cap with a previously characterized bioactive lipid antigen cocktail from Mycobacterium fortuitum, used as a surrogate source of antigens for tuberculosis diagnosis. After functionalization of the PDMS, the F-P sensors were immersed in different antibody-containing sera and the registered changes in their spectral features were associated to the interactions between the active lipids and the serum antibodies. Our results show that the proposed PDMS end-capped F-P immunosensors perform well differentiating antibody-containing sera. Furthermore, they offer attractive attributes such as label-free operation, real-time detection capabilities and they are also reusable. The proposed sensors, therefore, serve as an enabling optical immunosensing technique offering excellent potential for developing novel lipidomic analytical tools.

Identification of a novel anti‑heat shock cognate 71kDa protein antibody in patients with Kawasaki disease.

Kawasaki disease (KD) is an idiopathic form of acute systemic vasculitis, which clinically mimics febrile diseases. Although it has been hypothesized that immune system malfunction is associated with KD, its etiology remains unclear. The aim of the present study was to identify a KD-associated antibody. Immunoproteomic methods were used to identify KD-associated antigens that could be recognized in the sera of patients with KD. HeLa cells were used as an antigen source and KD sera were used as probe antibodies to determine the binding of the antibodies using an indirect immunofluorescence assay. Western blotting was performed to identify KD-associated antigens in HeLa whole cell lysates. Eight out of 12 serum samples obtained from patients with KD demonstrated immunoreactive bands at ~70 kDa, which was later determined to be heat shock cognate 71 kDa protein (HSP7C) by mass spectrometry. The diagnostic value of serum anti-HSP7C antibodies for KD was assessed using ELISA. Using a cut-off value of 0.267, anti-HSP7C antibodies were observed to be present in the sera of 60.00% (30/50) of patients with KD, in 21.05% (8/38) of non-KD febrile controls, and in 5.26% (2/38) of healthy controls. High serum levels of anti-HSP7C antibodies were detected in the peripheral circulation of patients with KD. To the best of our knowledge, the present study is the first to observe the high expression levels of anti-HSP7C antibodies in patients with KD. Therefore, anti-HSP7C antibodies may be used as a diagnostic marker to detect KD.

Breast cancer stem cell RNA-pulsed dendritic cells enhance tumor cell killing by effector T cells.

Cancer stem cells (CSCs) underpin the resistance of breast cancer (BC) cells to therapy. Dendritic cell (DC)-based treatment is efficacious and safe, but the efficiency of this technique for targeting CSCs in BC treatment requires further investigation. The present study aimed to investigate the ability of DCs pulsed with breast CSC antigens to activate effector lymphocytes for killing BC cells. CD44+/CD24− CSCs were isolated from BCA55-121, an in-house patient-derived BC cell line, and acquisition of stemness properties was confirmed by upregulated expression of OCT4A and a superior proliferative capacity in colony formation assays compared with whole population of BCA55-121 (BCA55-121-WP). DCs were differentiated from monocytes from peripheral blood of healthy donors and pulsed with CSC total RNA. Maturation of the CSC RNA-pulsed DCs was confirmed by increased expression of CD11c, CD40, CD83, CD86 and HLA-DR, as well as reduced CD14 expression compared with monocytes. Total lymphocytes co-cultured with CSC RNA-pulsed DCs were analyzed by flow cytometry for markers including CD3, CD4, CD8, CD16 and CD56. The results revealed that the co-cultures contained mostly cytotoxic CD8+ T lymphocytes followed by CD4+ T lymphocytes and smaller populations of natural killer (NK) and NKT cells. ELISA was used to measure IFN-γ production, and it was revealed that activated CD4+ and CD8+ lymphocytes produced more IFN-γ compared with naïve T cells, suggesting that CD8+ T cells were effector T cells. CSC RNA was a more efficient antigen source compared with RNA from mixed BC cells for activating tumor antigen-specific killing by T cells. These CSC-specific effector T cells significantly induced BC cell apoptosis at a 20:1 effector T cell:tumor cell ratio. Of note, the breast CSCs cultures demonstrated resistance to effector T cell killing, which was in part due to increased expression of programmed death ligand 1 in the CSC population. The present study highlights the potential use of CSC RNA for priming DCs in modulating an anticancer immune response against BC.

Development and Optimization of a GMP-Compliant Manufacturing Process for a Personalized Tumor Lysate Dendritic Cell Vaccine.

With the emergence of immune checkpoint inhibitors and adoptive T-cell therapies, there is a considerable interest in using personalized autologous dendritic cell (DC) vaccines in combination with T cell-targeting immunotherapies to potentially maximize the therapeutic impact of DC vaccines. Here, we describe the development and optimization of a Good Manufacturing Practice (GMP)-compliant manufacturing process based on tumor lysate as a tumor antigen source for the production of an oxidized tumor cell lysate loaded DC (OC-DC) vaccine. The manufacturing process required one day for lysate preparation and six days for OC-DC vaccine production. Tumor lysate production was standardized based on an optimal tumor digestion protocol and the immunogenicity was improved through oxidation using hypochloric acid prior to freeze-thaw cycles resulting in the oxidized tumor cell lysate (OC-L). Next, monocytes were selected using the CliniMACS prodigy closed system and were placed in culture in cell factories in the presence of IL-4 and GM-CSF. Immature DCs were loaded with OC-L and matured using MPLA-IFNγ. After assessing the functionality of the OC-DC cells (IL12p70 secretion and COSTIM assay), the OC-DC vaccine was cryopreserved in multiple doses for single use. Finally, the stability of the formulated doses was tested and validated. We believe this GMP-compliant DC vaccine manufacturing process will facilitate access of patients to personalized DC vaccines, and allow for multi-center clinical trials.

Detection of tumor antigens and tumor-antigen specific T cells in NSCLC patients: Correlation of the quality of T cell responses with NSCLC subtype

Allogeneic cancer cell lines serve as universal source of tumor-associated antigens in cancer vaccines. Immunogenic high hydrostatic pressure-killed cancer cells derived from cell lines can be used for the generation of dendritic cell (DC)-based active cellular immunotherapy of non-small cell lung cancer (NSCLC). We investigated the expression of 12 known NSCLC tumor-associated antigens (TAA) (CEA, MAGE-A1, MAGE-A3, MAGE-A4, PRAME, hTERT, HER2, MUC1, Survivin, STEAP1, SOX2 and NY-ESO-1) in 6 NSCLC cell lines as candidates for the generation of DC-based lung cancer vaccine. We showed that the selected antigenic profile of these cell lines overlaps to various degrees with that of primary NSCLC tumors (n = 52), indicating that 4 out of 6 NSCLC cell lines would be suitable for DC-based vaccine generation. We further investigated the presence of TAA-specific T cells in blood of NSCLC patients (n = 32) using commercially available peptide mixes in an in vitro stimulation assay. IFN-γ+CD8+ and IFN-γ+CD4+ T cell responses to all antigens were detected in NSCLC patients. Interestingly, despite higher TAA expression in squamous cell carcinoma (SCC) the responsiveness of patients’ T cells to stimulation was significantly lower in SCC patients than in adenocarcinoma (AC) patients. This suggests qualitative differences in T cell functionality between NSCLC subtypes. Based on this study, and in order to maximize the amount of treatable patients, we selected a mix of H520 and H522 NSCLC cell lines for DC-based vaccine preparation. We also established a minimal panel of antigenic peptide mixes (CEA, hTERT, PRAME, HER2) for immunomonitoring of T cell responses during the DC-based lung cancer immunotherapy in Phase I lung cancer clinical trial (NCT02470468).

PROSTATE-SPECIFIC ANTIGEN AND ITS MOLECULAR FORMS IN BLOOD SERUM OF HEALTHY WOMEN AND WOMEN WITH BREAST DISEASE

The purpose of the study was to provide data on the sources of prostate-specific antigen (Psa) in women, as well as on serum Psa levels in healthy women and in women with benign and malignant breast cancer. Material and methods. We analyzed 50 publications available from PubMed, Medline, Google scholar concerning non-prostatic sources of Psa and its use as a serum tumor-associated marker for benign and malignant breast tumors. Results. In our study, we focus on the recent findings on non-prostatic sources and regulation of Psa synthesis in women as well as on changes in serum concentrations of this marker in patients with benign and malignant breast tumors. Various Psa isoforms (total Psa and free Psa) and free/total ratio for the detection of breast cancer and the assessment of treatment response and early detection of breast cancer recurrence were analyzed. Conclusion . the results obtained highlight the value of the assessment of Psa isoforms for early detection, prediction of therapy response and detection of breast cancer relapse. However, further studies are needed to identify the role of Psa isoforms in the diagnosis and monitoring of breast cancer patients.