The Advantages of Multi-Epitope Tumor Antigens as an Approach to Treating Breast Cancer

2002 ◽  
Author(s):  
Syvia M. Kiertscher
Keyword(s):  
Cytokine ◽  
2011 ◽  
Vol 56 (1) ◽  
pp. 86-87
Author(s):  
Ramtin Rahbar ◽  
Albert Lin ◽  
Magar Ghazarian ◽  
Philipp Lang ◽  
Alisha R Elford ◽  
...  

Author(s):  
R. Kinders ◽  
J. Slota ◽  
J. Patrick ◽  
C. Plate ◽  
I. Kafer ◽  
...  
Keyword(s):  

2017 ◽  
Vol 10 (4) ◽  
pp. 327-334 ◽  
Author(s):  
Ruhollah Dorostkar ◽  
Mohammad Sadegh Hashemzadeh ◽  
Sajjad Jafari ◽  
Mahdi Tat ◽  
Majdedin Ghalavand ◽  
...  

Abstract Background Immunotherapy, during which the immune system of the patient is manipulated to act against tumors has been among the most successful methods in the treatment of breast cancer, a leading cause of mortality among women worldwide. Objectives To investigate the immunotherapeutic efficacy of Lactobacillus casei lysate as an adjuvant in combination with a heated-4T1 mammary carcinoma cell lysate in a model of breast cancer. Methods After ethics committee approval of all animal procedures, a murine model of breast cancer was induced in BALB/c mice using 4T1 cells. These mice were immunized with a combination of lysates of heated 4T1 cells and L. casei. Subsequent changes in tumor size and weight, and the production of TNF-α, IL-2, IL-12, IL-17, and IL13 were measured. Lung weights were measured as an indicator of metastasis to other organs. Results The tumor size and weight in mice immunized with the combined vaccine were significantly reduced compared with controls. The combined immunotherapy altered the pattern of cytokine production to the advantage of antitumor immunity, and was significantly more potent than immunization with heated-4T1-cell lysate or L. casei lysate alone. Conclusions Coadministration of L. casei lysate enhanced the immunotherapeutic efficacy of the heated-4T1-cell lysate as a source of tumor-associated antigens. L. casei can potentially be used as an adjuvant combined with sources of tumor antigens in the treatment of cancers, and as a safe alternative to the current adjuvants that cause greater irritation to hosts. Further studies are required to clarify the mechanisms underlying these effects.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Amirhossein Bahreyni ◽  
Yasir Mohamud ◽  
Honglin Luo

AbstractBreast cancer continues to be the most frequently diagnosed malignancy among women, putting their life in jeopardy. Cancer immunotherapy is a novel approach with the ability to boost the host immune system to recognize and eradicate cancer cells with high selectivity. As a promising treatment, immunotherapy can not only eliminate the primary tumors, but also be proven to be effective in impeding metastasis and recurrence. However, the clinical application of cancer immunotherapy has faced some limitations including generating weak immune responses due to inadequate delivery of immunostimulants to the immune cells as well as uncontrolled modulation of immune system, which can give rise to autoimmunity and nonspecific inflammation. Growing evidence has suggested that nanotechnology may meet the needs of current cancer immunotherapy. Advanced biomaterials such as nanoparticles afford a unique opportunity to maximize the efficiency of immunotherapy and significantly diminish their toxic side-effects. Here we discuss recent advancements that have been made in nanoparticle-involving breast cancer immunotherapy, varying from direct activation of immune systems through the delivery of tumor antigens and adjuvants to immune cells to altering immunosuppression of tumor environment and combination with other conventional therapies.


2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 31-31
Author(s):  
Gitte Pedersen

31 Background: In the context of diagnostics, RNA is proxy for proteins and proteins are typically targets for drugs; e.g. breast cancer is typically driven by over-expression of various hormone receptors and Her2. In the current standard-of-care setting there is no measurement of mutations. Furthermore, all the markers for response to the new immune therapies are expressed as mRNA. Approximately 15% of the breast cancer patients are triple negative. Due to the poor outcome of chemo, standard-of-care guidelines (NCCN) suggests doctors encourage the patient to enroll in clinical trials. However, with more than 2000 ongoing trials in breast, which trial could potentially benefit the patient? Methods: Using the RNA-seq data from the TCGA study, we analyzed more than 120 triple negative datasets. Results: We found at least one over-expressed checkpoint inhibitor target in almost all the patients, suggesting that if you analyzed for all of the checkpoint targets, it would be possible to find a clinical study for these patients. Furthermore, when we analyzed over-expressed tumor antigens, we realized that it would be possible to design sophisticated combination trials with this information. In addition, we identified patients that were BRCAwt with an impaired DNA repair pathway; e.g. some had BRCA silencing and could potentially benefit from PARP inhibitors. Finally, a small number of patients overexpressed the androgen receptor for which there is a drug approved for prostate cancer. Conclusions: Compared to DNA analysis, tumor RNA profiling has the potential to guide a much broader set of drugs and treatment approaches including immunotherapy and chemotherapy. Messenger RNA (mRNA) analysis can reveal tumor antigens and drug targets expressed by cancer cells, as well as the vital status of the tumor microenvironment including immune response, the integrity of DNA repair mechanisms, and the engagement of angiogenesis and other cancer-related pathways.


2010 ◽  
Vol 3 (1) ◽  
pp. 23-29
Author(s):  
Terry Lichtor

Antigenic differences between normal and malignant cells of the cancer patient form the rationale for clinical immunotherapeutic strategies. Because the antigenic phenotype of neoplastic cells varies widely among different cells within the same malignant cell-population, immunization with a vaccine that stimulates immunity to the broad array of tumor antigens expressed by the cancer cells is likely to be more efficacious than immunization with a vaccine for a single antigen. A vaccine prepared by transfer of DNA from the tumor into a highly immunogenic cell line can encompass the array of tumor antigens that characterize the patient’s neoplasm. Poorly immunogenic tumor antigens, characteristic of malignant cells, can become strongly antigenic if they are expressed by highly immunogenic cells. A DNA-based vaccine was prepared by transfer of genomic DNA from a breast cancer that arose spontaneously in a C3H/He mouse into a highly immunogenic mouse fibroblast cell line, where genes specifying tumor-antigens were expressed. The fibroblasts were modified in advance of DNA-transfer to secrete an immune augmenting cytokine and to express allogeneic MHC class I-determinants. In an animal model of breast cancer metastatic to the brain, introduction of the vaccine directly into the tumor bed stimulated a systemic cellular anti-tumor immune response measured by two independent in vitro assays and prolonged the lives of the tumor-bearing mice. Furthermore, using antibodies against the various T-cell subsets, it was determined that the systemic cellular anti-tumor immunity was mediated by CD8+, CD4+ and NK/LAK cells. In addition an enrichment strategy has also been developed to increase the proportion of immunotherapeutic cells in the vaccine which has resulted in the development of enhanced anti-tumor immunity. Finally regulatory T cells (CD4+CD25+Fox p3+-positive) were found to be relatively deficient in the spleen cells from the tumor-bearing mice injected intracerebrally with the enriched vaccine. The application of DNA-based genomic vaccines for the treatment of a variety of brain tumors is being explored.


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