Restoring Anti-Oncodriver Th1 Responses with Dendritic Cell Vaccines in HER2/
            <i>neu</i>
            -Positive Breast Cancer: Progress and Potential

Cruz, Lucy M. De La; Nocera, Nadia F.; Czerniecki, Brian J.

doi:10.2217/imt-2016-0052

Cited by 23 publications

(21 citation statements)

References 89 publications

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“…It has been revealed that infiltrating T cells and production of cytokines into tumor tissue is associated with improved clinical outcome in numerous types of cancers [ 7 , 10 ]. More specifically, T helper (Th) cells play central roles in the development of immune responses [ 11 ]. Recent studies have indicated that the balance between different CD4 + Th subsets (Th1, Th2, Th17, and Treg) is important in anti-tumor immunity, and perhaps, in the process of tumor progression [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Study of the tumor microenvironment during breast cancer progression

et al. 2017

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BackgroundDifferent cells and mediators in the tumor microenvironment play important roles in the progression of breast cancer. The aim of this study was to determine the composition of the microenvironment during tumor progression in order to discover new related biomarkers and potentials for targeted therapy.MethodsIn this study, breast cancer biopsies from four different stages, and control breast biopsies were collected. Then, the mRNA expression of several markers related to different CD4+ T cell subsets including regulatory T cells (Treg), T helper (Th) type 1, 2 and 17 were determined. In addition, we investigated the expression of two inflammatory cytokines (TNF-α and IL-6) and inflammatory mediators including FASL, IDO, SOCS1, VEGF, and CCR7.ResultsThe results showed that the expression of Th1 and Th17 genes was decreased in tumor tissues compared to control tissues. In addition, we found that the gene expression related to these two cell subsets decreased during cancer progression. Moreover, the expression level of TNF-α increased with tumor progression.ConclusionWe conclude that the expression of genes related to immune response and inflammation is different between tumor tissues and control tissues. In addition, this difference was perpetuated through the different stages of cancer.

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Section: Introductionmentioning

confidence: 99%

Study of the tumor microenvironment during breast cancer progression

et al. 2017

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“…The huge chapter of the immune adjuvants of endogen or exogen origin has to be deepened and may represent a major area of interest for the future. Immunotherapy is currently being tested for solid and hematological cancer from early to metastatic stage, with protocols involving it with an anxillary role or as a protagonist in cancer fighting for an increasing number of patients, eluding escaping variants ( 14 , 49 , 53 ). To let immunotherapy be the wished revolution in cancer therapy including BC, bioinformatics, drug design/pharmacology, molecular biology, data analysis, clinical science, and medical imaging will need to share an emerging mentality.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, T-cell stimulation aims to induce the activity of both T-helper and natural killer T cells. Strategies to increase Th1- (CD4 + ) and cytotoxic T-lymphocytes- (CTLs, CD8 + ) dependent immunity and to suppress Th1–Treg joined responses are currently being tested ( 14 ). This review will focus on the new perspectives for the use of BC vaccines ( 15 , 16 ), considering the ongoing clinical trials and the possible future perspectives to combine immunomodulation with other BC therapies.…”

Section: Introductionmentioning

confidence: 99%

Breast Cancer Vaccines: New Insights

et al. 2017

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Breast cancer (BC) is a persistent global challenge for its high frequency in women (although it seldom occurs in men), due to the large diffusion of risk factors and gene mutations, and for its peculiar biology and microenvironment. To date, BC can benefit from different therapeutic strategies involving surgery, ablation, chemotherapy, radiotherapy, and more specific approaches such as hormone therapy and the administration of various substances impairing cancer growth, aggressivity, and recurrence with different modalities. Despite these relatively wide chances, also used in combinatory protocols, relevant mortality and relapse rates, often associated with resistant phenotypes, stress the need for a personalized-medicine based on prompting the patient’s immune system (IS) against cancer cells. BC immunogenicity was latterly proven, so the whole immunotherapy field for BC is still at a very early stage. This immunotherapeutic approach exploits both the high specificity of adaptive immune response and the immunological memory. This review is focused on some of the majorly relevant BC vaccines available (NeuVax, AVX901, and INO-1400), providing a description of the more promising clinical trials. The efficacy of cancer vaccines highly depends on the patient’s IS, and a wide optimization is needed in terms of targets’ selection, drug design and combinations, dose finding, protocol structuring, and patients’ recruitment; moreover, new standards are being discussed for the outcome evaluation. However, early-phases excellent results suggest that the manipulation of the IS via specific vaccines is a highly attractive approach for BC.

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“…Interestingly, Czerniecki et al showed anti-HER2 CD4 + Th1 immunity to be a relevant component of HER2 + therapy, as loss of CD4 + Th1 responses correlated with poor prognosis and treatment responses 15 . The administration of a class II HER2 peptide-pulsed Type I polarized DC1 vaccine was shown to induce a strong anti-HER2 CD4 + Th1 response, with a pathologic complete response rate (pCR) among HER2 + ductal carcinoma in situ (DCIS) patients [69][70][71] .…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Clinical development of immunotherapies for HER2+ breast cancer: a review of HER2-directed monoclonal antibodies and beyond

Costa¹,

Czerniecki²

2020

npj Breast Cancer

129

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Human epidermal growth factor receptor 2-positive (HER2 +) breast cancer accounts for~25% of breast cancer cases. Monoclonal antibodies (mAbs) against HER2 have led to unparalleled clinical benefit for a subset of patients with HER2 + breast cancer. In this narrative review, we summarize advances in the understanding of immune system interactions, examine clinical developments, and suggest rationales for future investigation of immunotherapies for HER2 + breast cancer. Complex interactions have been found between different branches of the immune system, HER2 + breast cancer, and targeted treatments (approved and under investigation). A new wave of immunotherapies, such as novel HER2-directed mAbs, antibody drug conjugates, vaccines, and adoptive T-cell therapies, are being studied in a broad population of patients with HER2-expressing tumors. The development of immunotherapies for HER2 + breast cancer represents an evolving field that should take into account interactions between different components of the immune system.

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Restoring Anti-Oncodriver Th1 Responses with Dendritic Cell Vaccines in HER2/ neu -Positive Breast Cancer: Progress and Potential

Cited by 23 publications

References 89 publications

Study of the tumor microenvironment during breast cancer progression

Study of the tumor microenvironment during breast cancer progression

Breast Cancer Vaccines: New Insights

Clinical development of immunotherapies for HER2+ breast cancer: a review of HER2-directed monoclonal antibodies and beyond

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