Tumor antigenS heterogeneity and immune response-targeting neoantigens in breast cancer

Publication date: Available online 4 November 2019Source: Seminars in Cancer BiologyAuthor(s): Monica Benvenuto, Chiara Focaccetti, Valerio Izzi, Laura Masuelli, Andrea Modesti, Roberto BeiAbstractBreast cancer is both the most common type of cancer and the most frequent cause of cancer mortality in women, mainly because of its heterogeneity and limited immunogenicity. The aim of specific active cancer immunotherapy is to stimulate the host's immune response against cancer cells directly using a vaccine platform carrying one or more tumor antigens. In particular, the ideal tumor antigen should be able to elicit T cell and B cell responses, be specific for the tumor and be expressed at high levels on cancer cells. Neoantigens are ideal targets for immunotherapy because they are exclusive to individual patient’s tumors, are absent in healthy tissues and are not subject to immune tolerance mechanisms. Thus, neoantigens should generate a specific reaction towards tumors since they constitute the largest fraction of targets of tumor-infiltrating T cells.In this review, we describe the technologies used for neoantigen discovery, the heterogeneity of neoantigens in breast cancer and recent studies of breast cancer immunotherapy targeting neoantigens.
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research

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Cancer vaccines represent an active immunotherapy designed to stimulate the patient ’s immune system to recognize and kill tumor cells. Optimally, cancer vaccines stimulate type 1 CD4+ and CD8+T cell responses against tumor-associated antigens (Ags) (TAAs) and/or tumor specific Ags (TSAs) [1,2]. The main classes of TAAs and TSAs are summarized in Table 1. Known tumor Ags relevant to BC are shown in Table 2.
Source: Cancer Treatment Reviews - Category: Cancer & Oncology Authors: Tags: Tumour Review Source Type: research
Authors: Godoy-Calderón MJ, González-Marcano E, Carballo J, Convit AF Abstract Breast cancer therapies using checkpoints alone have not been highly effective. Based on previous experiences using the ConvitVax, an autologous tumor cells/bacillus Calmette-Guérin (BCG)/formalin-based vaccine, in breast cancer and the potential success of combined therapies, we sought to ascertain whether the ConvitVax combined with anti-PD-1 enhances the antitumor effect in a 4T1 breast cancer model. Animals received four weekly injections of either PBS (G1), ConvitVax (200 μg cell homogenate, 0.0625 mg BCG, 0....
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
We describe current and emerging combination approaches which may improve patient outcomes in metastatic breast cancer.
Source: Current Breast Cancer Reports - Category: Cancer & Oncology Source Type: research
ConclusionsThis case report describes the evolution of TiME and TNBC molecular subtypes/genomics over time with sequential therapies in a TNBC patient with a CR to atezolizumab monotherapy. These data suggest the TiME is pliable and may be manipulated to maximize response to immunotherapy (NCT01375842,https://clinicaltrials.gov/ct2/show/NCT01375842?term=NCT01375842&rank=1).
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
ConclusionsTaxanes were the most common tx choice for 1L mTNBC. Patient characteristics were similar among patients who received pac and nab-pac monotherapy, suggesting that they are prescribed interchangeably when reimbursed by insurance.Editorial acknowledgementMedical writing assistance for this abstract was provided by Chris Lum, PhD, of Health Interactions, and funded by F. Hoffmann-La Roche, Ltd.Legal entity responsible for the studyF. Hoffmann-La Roche, Ltd.FundingF. Hoffmann-La Roche, Ltd.DisclosureJ. O ’Shaughnessy: Honoraria (self): AbbVie Inc.; Honoraria (self): Agendia; Honoraria (self): Amgen Biotechnolo...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsThis first in human clinical trial of combination chemoradiation, cytokine fusion protein, checkpoint inhibitor, and NK cell therapy demonstrated a safe and tolerable immunotherapy protocol. Early efficacy data is encouraging with a 78% disease control rate, 56% ORR and 22% (2/9) CR in pts with metastatic TNBC, 2nd-line or greater.Clinical trial identificationNCT03387085.Legal entity responsible for the studyNantKwest, Inc.FundingNantKwest, Inc.DisclosureP. Soon-Shiong: Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: NantCell; Leadership role, Shareholder / Stockholder /...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsDevelopment of PD-1 B-cell vaccine was successful, showing no evidence of toxicity or autoimmunity in mice, rabbits and beagle dogs. The combination vaccines could provide improved outcomes in early stage disease sparing patients the toxicity of chemotherapy. A phase 1 clinical trial with the PD-1 vaccine is under planning.Legal entity responsible for the studyThe authors.FundingNIH; Imugene.DisclosureAll authors have declared no conflicts of interest.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Abstract Breast cancer, one of the leading causes of death in women in the United States, challenges therapeutic success in patients due to tumor heterogeneity, treatment resistance, metastasis and disease recurrence. Knowledge of immune system involvement in normal breast development and breast cancer has led to extensive research into the immune landscape of breast cancer and multiple immunotherapy clinical trials in breast cancer patients. However, poor immunogenicity and T-cell infiltration along with heightened immunosuppression in the tumor microenvironment have been identified as potential challenges to the...
Source: Advances in Cancer Research - Category: Cancer & Oncology Authors: Tags: Adv Cancer Res Source Type: research
Abstract Vaccines can be a cost effective preventive measure for both primary prevention of disease and prevention of disease recurrence. Several vaccines targeting breast cancer oncodrivers are currently being tested in clinical trials. Whereas clinical response rates to breast cancer vaccines have been modest despite the induction of strong antitumor T cell responses, it is through these approaches that valuable insight and knowledge have been gained about tumor immunology. With the emergence of new immunotherapies, there is renewed excitement for effective breast cancer vaccine development. PMID: 3107...
Source: Clinical Breast Cancer - Category: Cancer & Oncology Authors: Tags: Surg Oncol Clin N Am Source Type: research
Conclusion MTDH is pro-oncogenic factor playing multifaceted and diverse roles in cancer progression. Its association and central role in regulating signaling pathways such a MAPK, wnt/β-catenin, PI3K/AkT, NF-κβ pathways in various cancers shows that it plays a vital role in metastasis. MTDH contribution to chemo and radiotherapy resistance provides a new direction for the development of anticancer therapeutics. Multiple mechanisms converge to promote expression of MTDH in cancers. Further studies are therefore warranted to determine whether the elevated MTDH expression has prognostic value for development...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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