Breast Cancer Antigen Research Articles

Potential of PSMA for breast cancer in nuclear medicine: digital quantitative immunohistochemical analysis and implications for a theranostic approach

BackgroundFurther research is still needed to fully understand the potential of prostate-specific membrane antigen (PSMA) in breast cancer (BC) and to develop and optimize targeted therapies and imaging modalities. The objective of this study was to present a comprehensive analysis of immunohistochemistry data on PSMA staining in BC and to discuss its potential value in a theranostic approach.MethodsFifty-eight male and female patients were randomly selected from a retrospective database of patients who underwent surgery for breast cancer between January 2012 and December 2017 and for whom a specimen is available in our tumour library. Immunodetection of PSMA and CD31 was performed on serial slides. The digitized slides were reviewed and analysed by an experienced pathologist. Additionally, the corresponding TIFF images were processed to calculate the percentage of positive neovessels.ResultsEighteen patients (31.6%) had no expression, 29 (50.9%) had PSMA neovascular expression scored as “1”, and 10 (17.5%) had neovascular expression scored as “2”. Digital immunohistochemistry analysis for this last specific group of patients showed a median proportion of positive neovessels equal to 5% (range: 3–19). A multivariable logistic regression demonstrated that the odds of PSMA positivity were 4.55 times higher in non-luminal tumours and decreased by a factor of 0.12 in lobular subtypes. There was no association between sex or the presence of a germline BRCA1/2 mutation and PSMA expression in tumours.ConclusionsOur study highlights generally low neovascular expression of PSMA in specific histopathological subtypes of breast cancer, which will likely hamper the development of an adequate theranostic strategy.Trial registrationThe procedure has been retrospectively registered to the French National Institute for Health Data (N° F20220615153900).

B-309 Evaluation of the Analytical Performance of Breast and Ovarian Cancer Antigen Assays on the Atellica CI Analyzer

Abstract Background The Atellica® CI Analyzer is an automated, high-throughput integrated chemistry and immunoassay analyzer utilizing both Atellica® CH and Atellica® IM Assays. This study evaluated the analytical performance of the Atellica IM breast cancer antigen CA 15-3™ (CA 15-3) and the ovarian cancer antigen CA 125II™ (CA 125II) Assays on the Atellica CI Analyzer. Methods Precision studies were performed according to CLSI EP05-A3 using native and contrived human serum samples as well as contrived horse serum samples for CA 15-3. One aliquot of each sample pool was tested in duplicate in two runs per day ≥2 hours apart on each analyzer for ≥20 days. Precision studies were evaluated with one reagent lot on two systems. Method comparison studies were performed using three reagent lots according to CLSI EP09c. Individual native and contrived human serum samples were analyzed using the Atellica IM CA 15-3 and CA 125II Assays on the Atellica IM Analyzer and the Atellica CI Analyzer. LoB, LoD, and LoQ were determined as described in CLSI EP17-A2. Results Representative precision and method comparison results for each assay are listed in the table. For the two assays tested, repeatability and within-lab %CVs were <2.4% and <6.9%, respectively. Slopes determined by the weighted Deming linear regression model were approximately 1. Detection capability for the Atellica IM CA 15-3 Assay on the Atellica CI Analyzer was estimated to be 1.0 U/mL, 2.0 U/mL and 3.0 U/mL for LoB, LoD, and LoQ, respectively. When using the Atellica IM CA 125II Assay, detection capability was estimated to be 2.0 U/mL, 3.0 U/mL and 3.0 U/mL for LoB, LoD, and LoQ, respectively. Conclusions Evaluation of the Atellica IM CA 15-3 and CA 125II Assays using the Atellica CI Analyzer demonstrated good precision and equivalent performance compared to the same assays on the Atellica IM Analyzer.

Cosmetic implant placement in the female breast yields an altered local and systemic immune response: evidence for breast cancer immunosurveillance.

Women with cosmetic implants have lower rates of future breast cancer than the general population. We hypothesized the implant foreign body response could induce a local protective anti-cancer immunosurveillance. We expanded on our previous finding which showed women with breast implants have elevated antibody responses to certain breast cancer proteins. Blood samples and breast tissue were collected from women undergoing first time breast augmentation (implant-naive, IN) and revision breast augmentation (implant-exposed, IE). Sera were collected and antibody levels to common breast cancer proteins were quantified by enzyme-linked immunosorbent assay (ELISA). RT-PCR was performed on breast tissue samples to quantify immune-related gene expression levels between IN and IE. Bulk RNA sequencing was performed to identify differentially expressed genes and altered signaling pathways in the breasts of IN versus IE. In total, 188 patients were recruited (117 IN, 71 IE). Data demonstrated that IE patients had higher levels of antibodies to MUC-1, ER, and mammaglobin A compared to IN patients. MUC-1 expression was found to be higher in IE compared to IN breast tissue. RNA-seq analysis demonstrated upregulated pathways in IE breast tissue for B cell activation and development, Th2 related genes, T cell activation, chemotactic factors, and responses to estrogen. This is the first study to demonstrate that peri-implant inflammation extends beyond the implant capsule to breast parenchyma. Women with breast implants have more activated B cells in the breast parenchyma and elevated antibody responses to breast cancer antigen.

Breast cancer, viruses, and human leukocyte antigen (HLA)

Several viruses have been implicated in breast cancer, including human herpes virus 4 (HHV4), human herpes virus 5 (HHV5), human papilloma virus (HPV), human JC polyoma virus (JCV), human endogenous retrovirus group K (HERVK), bovine leukemia virus (BLV) and mouse mammary tumor virus (MMTV). Human leukocyte antigen (HLA) is involved in virus elimination and has been shown to influence breast cancer protection/susceptibility. Here we investigated the hypothesis that the contribution of a virus to development of breast cancer would depend on the presence of the virus, which, in turn, would be inversely related to the success of its elimination. For that purpose, we estimated in silico predicted binding affinities (PBA) of proteins of the 7 viruses above to 127 common HLA alleles (69 Class I [HLA-I] and 58 Class II HLA-II]) and investigated the association of these binding affinities to the breast cancer—HLA (BC-HLA) immunogenetic profile of the same alleles. Using hierarchical tree clustering, we found that, for HLA-I, viruses BLV, JCV and MMTV were grouped with the BC-HLA, whereas, for HLA-II, viruses BLV, HERVK, HPV, JCV, and MMTV were grouped with BC-HLA. Finally, for both HLA classes, the average PBAs of the viruses grouped with the BC-HLA profile were significantly lower than those of the other, non BC-HLA associated viruses. Assuming that low PBAs are likely associated with slower viral elimination, these findings support the hypothesis that a defective/slower elimination and, hence, longer persistence and inefficient/delayed production of antibodies against them underlies the observed association of the low-PBA group with breast cancer.

Analytical performance evaluation of breast and ovarian cancer antigen assays on the Atellica CI analyzer

Analytical performance evaluation of breast and ovarian cancer antigen assays on the Atellica CI analyzer

Prognostic Value of "Basal-like" Morphology, Tumor-Infiltrating Lymphocytes and Multi-MAGE-A Expression in Triple-Negative Breast Cancer.

"Basal-like" (BL) morphology and the expression of cancer testis antigens (CTA) in breast cancer still have unclear prognostic significance. The aim of our research was to explore correlations of the morphological characteristics and tumor microenvironment in triple-negative breast carcinomas (TNBCs) with multi-MAGE-A CTA expression and to determine their prognostic significance. Clinical records of breast cancer patients who underwent surgery between January 2017 and December 2018 in four major Croatian clinical centers were analyzed. A total of 97 non-metastatic TNBCs with available tissue samples and treatment information were identified. Cancer tissue sections were additionally stained with programmed death-ligand 1 (PD-L1) Ventana (SP142) and multi-MAGE-A (mAb 57B). BL morphology was detected in 47 (49%) TNBCs and was associated with a higher Ki-67 proliferation index and histologic grade. Expression of multi-MAGE-A was observed in 77 (79%) TNBCs and was significantly associated with BL morphology. Lymphocyte-predominant breast cancer (LPBC) status was detected in 11 cases (11.3%) and significantly correlated with the Ki-67 proliferation index, increased number of intratumoral lymphocytes (itTIL), and PD-L1 expression. No impact of BL morphology, multi-MAGE-A expression, histologic type, or LPBC status on disease-free survival was observed. Our data suggest that tumor morphology could help identify patients with potential benefits from CTA-targeting immunotherapy.

Assessment of Anti-Nuclear Antibodies and Anti-Extractable Nuclear Antigen Levels in Breast Cancer Patients

Anti-nuclear antibodies (ANAs) are autoantibodies synthesized in response to the cell nucleus contents and use as biomarkers of systemic autoimmune diseases. Inflammation, apoptosis and necrosis of the cells are consequences that accompany breast cancer against which autoantibodies will be produced. In this study, we aimed to evaluate the presence of ANAs and anti-extractable nuclear antigens (anti-ENAs) in breast cancer. A total of 33 luminal A and luminal B breast cancer patients were assessed for presence of ANAs and anti-ENAs. All the patients had received hormone therapy at least for 6 months before the tests. Patients were screened to ANAs by indirect immunofluorescence on human epithelial type 2 (HEp-2) cells. AESKUBLOTS® ANA-17 comp kit was used to identify the concentrations of U1-snRNP, snRNP/Sm, SmD1, dsDNA, SS-A/Ro 60, SS-A/Ro 52, SS-B/La antibodies. Fifteen (45.5%) patients were luminal A and 18 (54.5%) patients were luminal B. The median of age was 57 and the median of tumor size was 25. 19 (57.6%) patients had grade I or II and 14 (42.4%) had grade III. 3 patients had ANAs test positive. All the patients who had positive ANA test were luminal A breast cancer and had grade I or II tumors and positive lymph node, whereas, pathological tumor stage were varied. No statistically significant association was found between ANAs positivity and molecular subtype, age, body mass index (BMI), grade, tumor stage or lymph node involvement. Moreover, there were negative correlations between the anti-U1-snRNP and anti-dsDNA with Ki-67 and a correlation between anti-snRNP/Sm and anti-SS-A/Ro 52 was found. Comparing with luminal A, anti-U1-snRNP and anti-snRNP/Sm concentrations were statistically significantly lower in luminal B tumors (p= 0.015 and 0.016 respectively). Patients who had high grade tumors showed low concentrations of anti-snRNP/Sm (p=0.027), whereas patients who had lymph node metastasis showed high concentrations of anti-U1-snRNP (p=0.031). ANAs positivity was more common in luminal A breast cancer patients compared with luminal B. Anti-U1-snRNP and anti-snRNP/Sm concentrations were lower in luminal B. Moreover, patients who had high grade tumors showed low concentrations of anti-snRNP/Sm, whereas those who had lymph node metastasis showed high concentrations of anti-U1-snRNP.

Comparative study of electrochemical-based sensors and immunosensors in terms of advantageous features for detection of cancer biomarkers.

Cancer, becoming increasingly common globally, has a high mortality rate. Despite the much research on diagnosis and treatment methods, the benefits of technological developments, and newly developed sensor devices, cancer is still one of the leading causes of death worldwide. Early detection using powerful and noninvasive tools could be a future focus for prognosis and treatment follow-up. Therefore, electrochemical biosensors can be a strong choice for the detection of cancer biomarkers (such as alpha-fetoprotein, cytochrome c, prostate-specific antigen, myoglobin, carcinoembryonic antigen, alpha-fetoprotein, a cancer antigen, epidermal growth factor receptor, vascular endothelial growth factor, circulating tumor cell, and breast cancer antigen 1/2) due to their advantages such as high sensitivity, excellent selectivity, low cost, short analysis time, and simplicity. Furthermore, electrochemical biosensors are better suited for point-of-care applications due to their mass production and miniaturization ease. This review provides an overview of different electrochemical measurement techniques, bioreceptor surfaces, signal production and amplification, and the integration of electrochemical-modified sensors. Cancer biomarkers based on electrochemical biosensors were given in detail. In addition, studies with MIP-based sensors and immunosensors have been extensively discussed. Integrating electrochemical biosensors with cancer biomarkers was also emphasized as a new research trend. Finally, we provide an overview of current advances in measuring and analyzing cancer biomarkers using electrochemical biosensors and detail current challenges and future perspectives.

Immunosensor for breast cancer CD44 biomarker detection based on exfoliated graphene quantum dots integrated gold nanoparticles

Breast cancer is a fatal disease caused by the abnormal development of cells in the breast, which forms tumors, and whose progression results in metastatic behavior. In this study, we present a novel electrochemical immunosensor based on graphene quantum dots decorated gold nanoparticles (GQDs-GNPs) for the early detection of breast cancer antigen Cluster of Differentiation-44 (CD44). The GQDs have been synthesized through electrochemical exfoliation of waste dry cell batteries and a simple chemical process was employed for the synthesis of GQDs-GNPs nanocomposite. It has been characterized for its electrochemical properties. The immunosensor was created utilizing GQDs-GNPs nanocomposite cross-linked via EDC/NHS coupling procedure to immobilize anti-CD44 antibodies. The resultant electrode surface was characterized by Transmission Electron Microscopy (TEM), Cyclic Voltammetry (CV), Differential Pulse Voltammetry (DPV), and Electrochemical Impedance Spectroscopy (EIS). TEM analysis revealed an average spherical GQD size of 3 nm and a GNP size of 15 nm. In phosphate buffer saline (PBS), the immunosensor had a low detection limit of 1.17 fg/mL. The findings suggest that the generated GQDs-GNPs nanocomposite exhibits favorable properties for usage as a successful nanomaterial in biosensing and other applications. According to these findings, our newly built immunosensor has a lot of potential to be a valuable alternative diagnostic tool for identifying various cancer biomarkers, particularly CD44 that exist in biological materials. The results indicate that the synthesized GQDs-GNPs nanocomposite possesses desirable properties for use as an effective nanomaterial in biosensing and other applications.

Study on Clinicopathological Features and Risk Factors of Patients with Multiple Primary Breast Cancers and Thyroid Disease.

To explore the clinicopathological features and risk factors of patients with multiple primary breast cancers and thyroid disease. An analytic approach of the reviewing method was adopted to analyze the clinical data of 80 breast cancer patients who were admitted to our hospital from January 2020 to January 2022. They were divided into an observation group (breast cancer with thyroid lesions) and a control group (simple breast cancer) according to whether the clinical data were accompanied with thyroid lesions to compare the clinical characteristics, pathological types, staging characteristics, and molecular biological characteristics of the two groups and to research the risk factors of the two groups. (1) In the comparison of clinical data, the number of people aged ≥60 in the observation group was higher than that in the control group, and there was significant difference between the groups in the menopausal status data (P < 0.05). There was no statistical difference between the observation group and the control group in the comparison of clinical data of the body mass index, pregnancy frequency, labor frequency, and abortion history (P > 0.05). (2) In the comparison of pathological type and staging data, there was no statistical difference in the comparison of data on the pathological type, histological grade, T staging, N staging, and TNM staging between the observation group and the control group (P > 0.05). (3) In the comparison of data on molecular biology characteristics, there was a statistical difference in the nuclear proliferation antigen data between the observation group and the control group (P < 0.05). There was no statistical difference in the comparison of data on the estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, and molecular typing between the observation group and the control group (P > 0.05). (4) Logistic regression analysis showed that age, menopausal status, and nuclear proliferation antigen index were the high-risk inflammatory factors for combined thyroid lesions (P < 0.05). For patients with simple breast cancer, age, menopausal status, and nuclear proliferation antigen index are risk factors for combined thyroid lesions. Therefore, clinical attention should be paid to the above factors in the process of clinical treatment, and early-risk screening should be performed to achieve the purpose of improving the prognosis to the greatest extent.

Chemical Complementarity of Breast Cancer Resident, T-Cell Receptor CDR3 Domains and the Cancer Antigen, ARMC3, is Associated With Higher Levels of Survival and Granzyme Expression

Introduction: One of the most pressing goals for cancer immunotherapy at this time is the identification of actionable antigens. Methods: This study relies on the following considerations and approaches to identify potential breast cancer antigens: (i) the significant role of the adaptive immune receptor, complementarity determining region-3 (CDR3) in antigen binding, and the existence cancer testis antigens (CTAs); (ii) chemical attractiveness; and (iii) informing the relevance of the integration of items (i) and (ii) with patient outcome and tumor gene expression data. Results: We have assessed CTAs for associations with survival, based on their chemical complementarity with tumor resident T-cell receptor (TCR), CDR3s. Also, we have established gene expression correlations with the high TCR CDR3-CTA chemical complementarities, for Granzyme B, and other immune biomarkers. Conclusions: Overall, for several independent TCR CDR3 breast cancer datasets, the CTA, ARMC3, stood out as a completely novel, candidate antigen based on multiple algorithms with highly consistent approaches. This conclusion was facilitated by use of the recently constructed Adaptive Match web tool.

Identification of tumor antigens and immunogenic cell death-related subtypes for the improvement of immunotherapy of breast cancer.

The current immunotherapy strategy for breast cancer is limited. Tumor neoantigens have been proven to be a promising biomarker and potential target of immunotherapy in a variety of tumors. However, their effectiveness for breast cancer remains unclear. Immunogenic cell death (ICD) is a regulated form of cell death that can reshape the tumor immune microenvironment and activate adaptive immune responses. To this end, we screened potential antigens that could be used both for the development of immunotherapy and differentiating the patient-specific immune responses based on ICD-related risk signatures, in order to formulate an accurate scheme for breast cancer immunotherapy. We retrieved the gene expression profiles of the breast invasive cancer cohort and their corresponding clinical control data from The Cancer Genome Atlas. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to evaluate tumor antigen expression, the cBioPortal program was used to identify genetic variations, and the TIMER website was used to estimate the immune infiltration signatures. The risk score predictive model based on the ICD-related genes was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm, and the cohort was divided into low- and high-risk score groups. Two tumor antigens, namely, CCNE1 and PLK1, were associated with poor prognosis and infiltration of antigen-presenting cells. Furthermore, the ICD-related risk signature could significantly predict survival outcomes. The risk groups based on the ICD-related signature predictive model showed diverse immune infiltration and molecular and clinical features. The high-risk group was associated with low immune cell infiltration, immune score, expression of immune checkpoints, and human leukocyte antigen genes but high levels of CCNE1 and PLK1 and poor survival outcome. In conclusion, CCNE1 and PLK1 were identified as potential antigens in breast cancer. The ICD-related prognostic model distinguished immune response heterogeneity and predicted prognosis. Patients with high ICD-related risk scores were suitable to receive combination treatments based on CCNE1 or PLK1 and immune checkpoint inhibitors. In the future, these results will help us develop more accurate treatment schemes for patients with breast cancer.

Abstract P5-08-01: Globo H: A Globo series glycosphingolipid target antigen in breast cancer

Abstract Cancer cells may be differentiated from normal cells by the surface expression of unusual glycosylation patterns: tumor-associated carbohydrate antigens (TACAs) may be expressed as membrane-bound glycoproteins or glycolipids. Differential expression of TACAs in multiple cancer types represents a potential therapeutic target for anticancer therapies. At least 16 different types of epithelial cancers have been found to be Globo H–positive, with 60% to 65% of patients with breast cancer having Globo H–positive tumors. It has been shown that tumor-infiltrating lymphocytes in breast cancer tissues could take up Globo H ceramide (GHCer) released by tumor cells masking cancer cells from immune surveillance through the suppression of Notch 1 signaling. Globo series antigens, including Globo H and stage-specific embryonic antigen 4 could associate with the FAK/CAV1/AKT/RIP complex to trigger the downstream β-catenin signaling pathway to promote tumor cell survival. Moreover, exogenous addition of GHCer promoted tumor cell migration. Thus, treatment-mediated depletion of GHCer may overcome the immunosuppressive mechanism of cancer cells, with resulting decreases in tumor cell survival and migration. OBI Pharma, Inc., in collaboration with NeoGenomics, has developed a validated immunohistochemistry assay to measure the expression of Globo H in clinical specimens. The intensity and extent of Globo H expression are determined microscopically using the histochemical scoring system (H-score), defined as the sum of the products of the staining intensity (score of 0-3) multiplied by the percentage of cells (0-100) stained at a given intensity. To date, 420 patients with triple-negative breast cancer (TNBC) have been screened across 4 separate clinical trials. Of those patients, 173 (41%) had an H-score of ≥15, with a median H-score of 70. Of the 173 patients with an H-score of ≥15, 69 (40%) had an H-score of ≥100. Adagloxad simolenin (AS/OBI-822) is a Globo H conjugate vaccine that when administered in combination with the adjuvant OBI-821 results in anti–Globo H IgM and IgG humoral immune responses. These responses have been assessed in all clinical trials of AS/OBI-821 to date. In the early trials that administered up to 9 doses, early and robust IgM responses were noted but with delayed and lower-titer IgG responses. When the number of doses was increased to 9-12 doses over an extended time (up to either 37 or 68 weeks), it became apparent that the peak IgG titers occurred at around the time of the last AS/OBI-821 dose. The time course for the development of anti–Globo H IgM and IgG humoral responses showed that following injection, anti–Globo H IgM and IgG antibody titers demonstrated a geometric mean ratio (GMR) increase of 10.26 and 12.47, respectively, from almost nondetectable levels at baseline. The GMR in the placebo group remained low in comparison. Mean time to peak titer was approximately 4 weeks for IgM and 40 weeks for IgG. These data were employed in the design of the phase 3, randomized, open-label study of the anti–Globo H vaccine AS/OBI-821 in the adjuvant treatment of patients with high-risk, early-stage Globo H–positive TNBC (The GLORIA Study). To enter the GLORIA study, patients must have a centrally confirmed Globo H IHC H-score of ≥15, and it is anticipated that approximately 40% of patients screened will have this level of expression. The GLORIA study is presently enrolling patients in 7 countries, with another 9 countries anticipated to begin recruiting in 2021. Citation Format: Darren S. Sigal, Apostolia Maria Tsimberidou, I-Ju Chen, Pei Hsu, Tillman Pearce. Globo H: A Globo series glycosphingolipid target antigen in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-08-01.

CAR-T Cell Therapy for Breast Cancer: From Basic Research to Clinical Application

Breast cancer rises as the most commonly diagnosed cancer in 2020. Among women, breast cancer ranks first in both cancer incidence rate and mortality. Treatment resistance developed from the current clinical therapies limits the efficacy of therapeutic outcomes, thus new treatment approaches are urgently needed. Chimeric antigen receptor (CAR) T cell therapy is a type of immunotherapy developed from adoptive T cell transfer, which typically uses patients' own immune cells to combat cancer. CAR-T cells are armed with specific antibodies to recognize antigens in self-tumor cells thus eliciting cytotoxic effects. In recent years, CAR-T cell therapy has achieved remarkable successes in treating hematologic malignancies; however, the therapeutic effects in solid tumors are not up to expectations including breast cancer. This review aims to discuss the development of CAR-T cell therapy in breast cancer from preclinical studies to ongoing clinical trials. Specifically, we summarize tumor-associated antigens in breast cancer, ongoing clinical trials, obstacles interfering with the therapeutic effects of CAR-T cell therapy, and discuss potential strategies to improve treatment efficacy. Overall, we hope our review provides a landscape view of recent progress for CAR-T cell therapy in breast cancer and ignites interest for further research directions.

Glycolipid-peptide conjugate vaccines elicit CD8+ T-cell responses and prevent breast cancer metastasis.

ObjectivesMetastasis is the principal cause of breast cancer mortality. Vaccines targeting breast cancer antigens have yet to demonstrate clinical efficacy, and there remains an unmet need for safe and effective treatment to reduce the risk of metastasis, particularly for people with triple‐negative breast cancer (TNBC). Certain glycolipids can act as vaccine adjuvants by specifically stimulating natural killer T (NKT) cells to provide a universal form of T‐cell help.MethodsWe designed and made a series of conjugate vaccines comprising a prodrug of the NKT cell‐activating glycolipid α‐galactosylceramide covalently linked to tumor‐expressed peptides, and assessed these using E0771‐ and 4T1‐based breast cancer models in vivo. We employed peptides from the model antigen ovalbumin and from clinically relevant breast cancer antigens HER2 and NY‐ESO‐1.ResultsGlycolipid‐peptide conjugate vaccines that activate NKT cells led to antigen‐presenting cell activation, induced inflammatory cytokines, and, compared with peptide alone or admixed peptide and α‐galactosylceramide, specifically enhanced CD8+ T‐cell responses against tumor‐associated peptides. Primary tumor growth was delayed by vaccination in all tumor models. Using 4T1‐based cell lines expressing HER2 or NY‐ESO‐1, a single administration of the relevant conjugate vaccine prevented tumor colonisation of the lung following intravenous inoculation of tumor cells or spontaneous metastasis from breast, respectively.ConclusionGlycolipid‐peptide conjugate vaccines that activate NKT cells prevent lung metastasis in breast cancer models and warrant investigation as adjuvant therapies for high‐risk breast cancer.

Expression of Prostate Specific Membrane Antigen (PSMA) in Breast Cancer.

Background Prostate specific membrane antigen (PSMA) is a promising protein for breast cancer patients. It has not only been detected in prostate cancer but is also expressed by tumor cells and the endothelial cells of tumor vessels in breast cancer patients. PSMA plays a role in tumor progression and tumor angiogenesis. For this reason, a number of diagnostic and therapeutic methods to target PSMA have been developed. Method This paper provides a general structured overview of PSMA and its oncogenic potential, with a special focus on its role in breast cancer. This narrative review is based on a selective literature search carried out in PubMed and the library of Freiburg University Clinical Center. The following key words were used for the search: “PSMA”, “PSMA and breast cancer”, “PSMA PET/CT”, “PSMA tumor progression”. Relevant articles were explicitly read through, processed, and summarized. Conclusion PSMA could be a new diagnostic and therapeutic alternative, particularly for triple-negative breast cancer. It appears to be a potential predictive and prognostic marker.

Serological Changes of Monoclonal Antibody CAMA3C8 against Human Breast Cancer Cell Line

Background: Tumor associated antigen are glycoproteins and glycolipids expressed on the surface or in the cytoplasm of tumor cells. The antigenic components are shed from the tumor cells into the tissue culture medium or blood or other human body fluids like human milk.&#x0D; Objective: In the present study, investigate the serological assay of the antigen recognized by CAMA3C8 in patients with carcinoma of the breast.&#x0D; Methods: The study is desgriptive cross section study.The study was divited into four groups based on the expression of tumor associated antigen.&#x0D; Results: In breast cancer CAMA3C8 levels were significantly increased in stage 4 when compared with stage 1 breast cancer cell line. &#x0D; Conclusion: In the present study, we conclude that significantly recognized CAMA3C8 defined antigens in breast cancer.

Breast Implants and Breast Cancer Immunosurveillance: An Updated Analysis of Serum Antibody Responses to Breast Cancer Antigen Post Implant Placement

Breast Implants and Breast Cancer Immunosurveillance: An Updated Analysis of Serum Antibody Responses to Breast Cancer Antigen Post Implant Placement

Co-Stimulatory Bispecific Antibodies Induce Enhanced T Cell Activation and Tumor Cell Killing in Breast Cancer Models.

Although T cell-recruiting CD3-binding bispecific antibodies (BiMAb) have been proven to be clinically effective for hematologic malignancies, the success of BiMAb targeting solid tumor-associated antigens (TAA) in carcinomas so far remains poor. We reasoned that provision of co-stimulatory BiMAb in combination with αTAA–αCD3 BiMAb would boost T cell activation and proliferative capacity, and thereby facilitate the targeting of weakly or heterogeneously expressed tumor antigens. Various αTAA–αCD3 and αTAA–αCD28 BiMAb in a tetravalent IgG1-Fc based format have been analyzed, targeting multiple breast cancer antigens including HER2, EGFR, CEA, and EpCAM. Moreover, bifunctional fusion proteins of αTAA–tumor necrosis factor ligand (TNFL) superfamily members including 4-1BBL, OX40L, CD70 and TL1A have been tested. The functional activity of BiMAb was assessed using co-cultures of tumor cell lines and purified T cells in monolayer and tumor spheroid models. Only in the presence of tumor cells, αTAA–αCD3 BiMAb activated T cells and induced cytotoxicity in vitro, indicating a strict dependence on cross-linking. Combination treatment of αTAA–αCD3 BiMAb and co-stimulatory αTAA–αCD28 or αTAA–TNFL fusion proteins drastically enhanced T cell activation in terms of proliferation, activation marker expression, cytokine secretion and tumor cytotoxicity. Furthermore, BiMAb providing co-stimulation were shown to reduce the minimally required dose to achieve T cell activation by at least tenfold. Immuno-suppressive effects of TGF-β and IL-10 on T cell activation and memory cell formation could be overcome by co-stimulation. BiMAb-mediated co-stimulation was further augmented by immune checkpoint-inhibiting antibodies. Effective co-stimulation could be achieved by targeting a second breast cancer antigen, or by targeting fibroblast activation protein (FAP) expressed on another target cell. In tumor spheroids derived from pleural effusions of breast cancer patients, co-stimulatory BiMAb were essential for the activation tumor-infiltrating lymphocytes and cytotoxic anti-tumor responses against breast cancer cells. Taken together we showed that co-stimulation significantly potentiated the tumoricidal activity of T cell-activating BiMAb while preserving the dependence on TAA recognition. This approach could provide for a more localized activation of the immune system with higher efficacy and reduced peripheral toxicities.

Serum Human Epididymis Protein-4 (HE4) - A novel Approach to Differentiate Malignant Frombenign Breast Tumors.

Background:The lack of sensitivity and specificity of existing diagnostic markers like Carbohydrate Antigen 15-3(CA15-3) and Carcinoembryonic antigen (CEA) in breast cancer stimulates the search for new biomarkers to improve diagnostic sensitivity especially in differentiating benign and malignant breast tumors. Expression of Human epididymal protein 4 (HE4) has been demonstrated in ductal carcinoma of the breast tissue. So we tried to evaluate serum HE4 levels as diagnostic marker in breast cancer patients and to comparatively assess serum HE4, CEA and CA15-3 in breast tumor patients both benign and malignant. Methods:Total 90 female subjects were included in the study. We selected 30 breast cancer cases (Malignant group) and 30 benign breast lump cases (Benign group) based on histopathology report. And other 30 were age matched apparently healthy controls (Control group). HE4, CEA and CA15-3 were analysed in serum samples of all subjects by Electrochemiluminiscence immunoassay method. Results:A significant difference in the median (IQR) of HE4 (pmol/l) was identified among malignant, benign and control groups {62.4(52.6-73.7) vs 49.3(39.8-57.4) vs 52.3(50.6-63.3) P=0.0009} respectively. The cutoff value for prediction of breast cancer was determined at >54.5 pmol/l for HE4, with a sensitivity of 73.3%, specificity of 65.3%, whereas cutoff value of CA 15-3 was >21.24 (U/ml) with a sensitivity of 56.7%, specificity of 74.5%. For CEA at cutoff value >0.99 (ng/ml) the sensitivity and specificity were 96.7 % and 62.7% respectively. AUC for HE4, CA15-3 and CEA were 0.725, 0.644 and 0.857 respectively. Conclusion:Our study demonstrated that serum levels of HE4 were significantly higher in malignant group compared to benign and control groups. There is no significant difference between HE4 levels between benign and control groups. These results indicate that HE4 appears as a useful and highly specific biomarker for breast cancer, which can differentiate between malignant and benign tumors.