B19-VLPs as an effective delivery system for tumour antigens to induce humoral and cellular immune responses against triple negative breast cancer

2021 ◽  
Author(s):  
Ángel de Jesús Jiménez-Chávez ◽  
Brenda Katherine Nava-García ◽  
Ismael Bustos Jaimes ◽  
Leticia Moreno-Fierros
Keyword(s):  
Breast Cancer ◽  
Immune Responses ◽  
Delivery System ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cellular Immune Responses ◽  
Effective Delivery ◽  
Tumour Antigens ◽  
Cellular Immune

scholarly journals A self-assembled RNA-triple helix hydrogel drug delivery system targeting triple-negative breast cancer

2020 ◽  
Vol 8 (16) ◽  
pp. 3527-3533 ◽  
Author(s):  
Lairong Ding ◽  
Junwei Li ◽  
Changrong Wu ◽  
Feng Yan ◽  
Xuemei Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Triple Negative Breast Cancer ◽  
Triple Helix ◽  
Triple Negative ◽  
Breast Cancers ◽  
Self Assembled ◽  
Rna Triple Helix

A novel RNA-triple-helix hydrogel for treatment of triple negative breast cancers (TNBCs) by incorporating RNA-triple-helix and siRNA duplexes of CXCR4 into the same RNA nanoparticles was developed, without the synthetic polycationic reagents.

scholarly journals Study and Preparation of Multifunctional Poly(L-Lysine)@Hyaluronic Acid Nanopolyplexes for the Effective Delivery of Tumor Suppressive MiR-34a into Triple-Negative Breast Cancer Cells

Materials ◽  
2020 ◽  
Vol 13 (23) ◽  
pp. 5309
Author(s):  
Jamila Djafari ◽  
Javier Fernández-Lodeiro ◽  
Hugo M. Santos ◽  
Julia Lorenzo ◽  
Sergi Rodriguez-Calado ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hyaluronic Acid ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Viral Gene ◽  
Tnbc Cell Line ◽  
Effective Delivery ◽  
Potential Strategy ◽  
Microrna Delivery ◽  
Viral Gene Delivery

Non-viral gene delivery using exogenous microRNAs is a potential strategy for fighting cancers with poor prognosis and which lack specific therapies, such as triple-negative breast cancer (TNBC). Herein we report the synthesis of six nontoxic electrostatic polymeric nanocapsules (P1 to P6) for microRNA delivery in TNBC cells. 1H Nuclear Magnetic Resonance (NMR) spectroscopy and Scanning Electron Microscopy (SEM) were used to characterize the nanopolyplexes, synthesized with Poly(L-Lysine) and hyaluronic acid (Ha). Studies on the activity of the ternary HA/PLI/miRNA-34 nanopolyplexes towards TNBC cell line MDA-MB-231 were conducted. The nanopolyplexes mediated intracellular restoration of tumor suppressor miR34a was evaluated by using Western blotting to quantify the expression level of the Bcl-2 protein. The results suggest that the P5, with a ratio PLI/Ha of 0.05, was the most promising for the delivery of miR-34a into TNBC cells; the P5 nanocapsules were able to reduce Bcl-2 expression at a protein level, and had an effect in the overall cell viability after 24 h treatment.

Lignin-graft-PLGA drug-delivery system improves efficacy of MEK1/2 inhibitors in triple-negative breast cancer cell line

Nanomedicine ◽  
2020 ◽  
Vol 15 (10) ◽  
pp. 981-1000
Author(s):  
C Ethan Byrne ◽  
Carlos E Astete ◽  
Manibarathi Vaithiyanathan ◽  
Adam T Melvin ◽  
Mahsa Moradipour ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cell Line ◽  
Drug Delivery System ◽  
Delivery System ◽  
Triple Negative Breast Cancer ◽  
Targeted Therapies ◽  
Triple Negative ◽  
Mesenchymal Transition

Aim: Few targeted therapies are available for triple-negative breast cancer (TNBC) patients. Here, we propose a novel alkaline-lignin-conjugated-poly(lactic- co-glycolic acid) (L-PLGA) nanoparticle drug delivery system to improve the efficacy of targeted therapies. Materials & methods: L-PLGA nanoparticles (NPs) loaded with the MEK1/2 inhibitor GDC-0623 were characterized, tested in vitro on MDA-MB-231 TNBC cell line and compared with loaded PLGA NPs. Results: Loaded L-PLGA NPs were less than half the size of PLGA NPs, had slower drug release and improved the efficacy of GDC-0623 when tested in vitro. We demonstrated that GDC-0623 reversed epithelial-to-mesenchymal transition in TNBC. Conclusion: Our findings indicate that L-PLGA NPs are superior to PLGA NPs in delivering GDC-0623 to cancer cells for improved efficacy in vitro.

Improved tumor targeting and penetration by a dual-functional poly(amidoamine) dendrimer for the therapy of triple-negative breast cancer

2019 ◽  
Vol 7 (23) ◽  
pp. 3724-3736 ◽  
Author(s):  
Changliang Liu ◽  
Houqian Gao ◽  
Zijian Zhao ◽  
Iman Rostami ◽  
Chen Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Triple Negative Breast Cancer ◽  
Tumor Targeting ◽  
Triple Negative ◽  
Pamam Dendrimer ◽  
Tat Peptide ◽  
Dual Functional

A dual-functional drug delivery system based on the conjugation of PAMAM dendrimer with EBP-1 and TAT peptide was established for the therapy of triple-negative breast cancer.

Boosting immune responses against early breast cancer

2020 ◽  
Vol 12 (535) ◽  
pp. eabb2773
Author(s):  
Ecaterina Ileana-Dumbrava
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Immune Responses ◽  
Early Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Therapeutic Responses

Pembrolizumab combined with neoadjuvant chemotherapy improves therapeutic responses in patients with early triple-negative breast cancer.

scholarly journals Neoantigen DNA vaccines are safe, feasible, and capable of inducing neoantigen-specific immune responses in patients with triple negative breast cancer

2021 ◽  
Author(s):  
Xiuli Zhang ◽  
S. Peter Goedegebuure ◽  
Nancy Myers ◽  
Tammy Vickery ◽  
Michael McLellan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Immune Responses ◽  
Dna Vaccine ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Dna Vaccines ◽  
Laboratory Evaluation ◽  
Minimal Risk ◽  
Free Survival

PURPOSE: Cancer neoantigens are important targets of cancer immunotherapy. Neoantigen vaccines have the potential to induce or enhance highly specific antitumor immune responses with minimal risk of autoimmunity. We have developed a neoantigen DNA vaccine platform capable of efficiently presenting both HLA class I and II epitopes. To test the safety, feasibility and efficacy of this platform, we performed a phase 1 clinical trial in triple negative breast cancer patients with persistent disease following neoadjuvant chemotherapy, a patient population at high risk of disease recurrence. EXPERIMENTAL DESIGN: Expressed somatic mutations were identified by tumor/normal exome sequencing and tumor RNA sequencing. The pVACtools software suite was used to identify and prioritize cancer neoantigens. Neoantigen DNA vaccines were designed and manufactured in an academic GMP facility at Washington University School of Medicine. Neoantigen DNA vaccines were administered via electroporation following completion of standard of care therapy. Safety was measured by clinical and laboratory evaluation. Immune responses were assessed by ELISPOT, flow cytometry and TCR sequencing. RESULTS: 18 subjects received three doses of a personalized neoantigen DNA vaccine encoding on average 11 neoantigens per patient (range 4-20). The vaccinations were well tolerated with limited adverse events, primarily related to injection site reactions. Neoantigen-specific immune responses were induced in 16/18 patients as measured by ELISPOT and flow cytometry. At a median follow-up of 36 months, progression-free survival was 87.5% (95% CI: 72.7-100%) in the cohort of vaccinated patients compared to 49% (95% CI: 36.4-65.9%) in a cohort of institutional historical control patients (p=0.011). CONCLUSIONS: Neoantigen DNA vaccines are safe, feasible, and capable of inducing a neoantigen-specific immune response. There is preliminary evidence of improved disease-free survival compared to historical controls.

scholarly journals Immunomodulating Therapies in Breast Cancer—From Prognosis to Clinical Practice

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4883
Author(s):  
Marcus Schmidt ◽  
Anne-Sophie Heimes
Keyword(s):  
Breast Cancer ◽  
Immune Responses ◽  
Triple Negative Breast Cancer ◽  
Immune Checkpoint ◽  
Triple Negative ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Tumor Infiltrating Lymphocytes ◽  
Response To Chemotherapy ◽  
Infiltrating Lymphocytes

The role of the immune system in breast cancer has been debated for decades. The advent of technologies such as next generation sequencing (NGS) has elucidated the crucial interplay between somatic mutations in tumors leading to neoantigens and immune responses with increased tumor-infiltrating lymphocytes and improved prognosis of breast cancer patients. In particular, triple-negative breast cancer (TNBC) has a higher mutational burden compared to other breast cancer subtypes. In addition, higher levels of tumor-associated antigens suggest that immunotherapies are a promising treatment option, specifically for TNBC. Indeed, higher concentrations of tumor-infiltrating lymphocytes are associated with better prognosis and response to chemotherapy in TNBC. An important target within the cancer immune cell cycle is the “immune checkpoint”. Immune checkpoint inhibitors (ICPis) block the interaction of certain cell surface proteins that act as “brakes” on immune responses. Recent studies have shown that ICPis improve survival in both early and advanced TNBC. However, this comes at the price of increased toxicity, particularly immune-mediated toxicity. As an alternative approach, individualized mRNA vaccination strategies against tumor-associated neoantigens represent another promising approach leading to neoantigen-specific immune responses. These novel strategies should help to improve treatment outcomes, especially for patients with triple negative breast cancer.

An aluminum adjuvant-integrated nano-MOF as antigen delivery system to induce strong humoral and cellular immune responses

2019 ◽  
Vol 300 ◽  
pp. 81-92 ◽  
Author(s):  
Xiaofang Zhong ◽  
Yunting Zhang ◽  
Lu Tan ◽  
Tao Zheng ◽  
Yingying Hou ◽  
...  
Keyword(s):  
Immune Responses ◽  
Delivery System ◽  
Antigen Delivery ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals The Synthesis of Glutamine-Functionalized Block Polymer and Its Application in Triple-Negative Breast Cancer Treatment

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yi-Zhi Zhu ◽  
Di Xu ◽  
Zhen Liu ◽  
Tian Tian ◽  
Fei Deng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Triple Negative Breast Cancer ◽  
Tumor Targeting ◽  
Triple Negative ◽  
Drug Carrier ◽  
Block Polymer

Triple-negative breast cancer (TNBC) is a highly malignant tumor. At present, there are still no targeted drugs for TNBC. Clinical chemotherapeutic drugs, such as doxorubicin (DOX), have the characteristic of nontargeted distribution in treatment of TNBC, causing severe side effects. Therefore, new target treatment strategies for TNBC are of urgent need. It was speculated that glutamine could be a potential target because it is in high demand by TNBC. In this study, we found that the transporter for glutamine, ASCT2 (solute carrier family 1 member 5 (SLC1A5)), is highly expressed in TNBC by analysis of data from The Cancer Genome Atlas (TCGA) and experiments in vitro. Based on this, glutamine was grafted onto a polymeric drug carrier in order to develop a tumor-targeting drug delivery system for treatment of TNBC. Firstly, pH-responsive glutamine-PEG5000-b-PAE10000 (Gln-PEG-b-PAE) copolymers were synthesized using Fmoc-PEG5000-b-PAE10000 (Fmoc-PEG-b-PAE) copolymers. Then, Gln-PEG-b-PAE@DOX micelles were prepared by loading DOX to Gln-PEG-b-PAE copolymer using a solvent casting technology. In vitro, Gln-PEG-b-PAE@DOX micelles exhibited pH-dependent micellization-decellularization behavior; namely, they can rapidly release DOX in acidic environment of pH 6.0 but release very slowly in physiological condition. Moreover, glutamine competition experiment showed that Gln-PEG-b-PAE@DOX micelles had the ability to target MDA-MB-231 cells. Compared to free DOX, Gln-PEG-b-PAE@DOX micelles had significantly greater cytotoxic effect and antiproliferative activity against MDA-MB-231 cells. In vivo, compared to free DOX and mPEG-b-PAE@DOX micelles, Gln-PEG-b-PAE@DOX micelles significantly inhibited tumor growth in tumor-bearing mice. Therefore, Gln-PEG-b-PAE@DOX micelles, as a tumor-targeting drug delivery system, may provide a new method for the treatment of TNBC.

Sign in / Sign up

Export Citation Format

Share Document