Current status of autologous breast tumor cell-based vaccines

Kurtz, Samantha L.; Ravindranathan, Sruthi; Zaharoff, David A.

doi:10.1586/14760584.2014.969714

Cited by 22 publications

(19 citation statements)

References 41 publications

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“…For breast cancer, ATCV clinical studies have been limited to three completed [ 44 – 46 ] and two active trials [ 47 , 48 ]. All three completed studies show promise in generating antitumor responses [ 49 ]. Despite the relatively small number of clinical studies, breast cancer remains an ideal indication for ATCV deployment as (1) 62% of breast cancer cases are diagnosed at stage I, where the tumor is still localized in the breast with minimal impact on the patient’s immune status [ 50 ]; (2) nearly all patients with breast cancer undergo tumor resection, thus ensuring a source of tumor cells for ATCV production; and (3) the vast majority of patients with breast cancer have minimal, if any, detectable disease after resection so the tumor burden is low.…”

Section: Introductionmentioning

confidence: 99%

Tumor-derived granulocyte colony-stimulating factor diminishes efficacy of breast tumor cell vaccines

et al. 2018

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BackgroundAlthough metastasis is ultimately responsible for about 90% of breast cancer mortality, the vast majority of breast-cancer-related deaths are due to progressive recurrences from non-metastatic disease. Current adjuvant therapies are unable to prevent progressive recurrences for a significant fraction of patients with breast cancer. Autologous tumor cell vaccines (ATCVs) are a safe and potentially useful strategy to prevent breast cancer recurrence, in a personalized and patient-specific manner, following standard-of-care tumor resection. Given the high intra-patient and inter-patient heterogeneity in breast cancer, it is important to understand which factors influence the immunogenicity of breast tumor cells in order to maximize ATCV effectiveness.MethodsThe relative immunogenicity of two murine breast carcinomas, 4T1 and EMT6, were compared in a prophylactic vaccination-tumor challenge model. Differences in cell surface expression of antigen-presentation-related and costimulatory molecules were compared along with immunosuppressive cytokine production. CRISPR/Cas9 technology was used to modulate tumor-derived cytokine secretion. The impacts of cytokine deletion on splenomegaly, myeloid-derived suppressor cell (MDSC) accumulation and ATCV immunogenicity were assessed.ResultsMice vaccinated with an EMT6 vaccine exhibited significantly greater protective immunity than mice vaccinated with a 4T1 vaccine. Hybrid vaccination studies revealed that the 4T1 vaccination induced both local and systemic immune impairments. Although there were significant differences between EMT6 and 4T1 in the expression of costimulatory molecules, major disparities in the secretion of immunosuppressive cytokines likely accounts for differences in immunogenicity between the cell lines. Ablation of one cytokine in particular, granulocyte-colony stimulating factor (G-CSF), reversed MDSC accumulation and splenomegaly in the 4T1 model. Furthermore, G-CSF inhibition enhanced the immunogenicity of a 4T1-based vaccine to the extent that all vaccinated mice developed complete protective immunity.ConclusionsBreast cancer cells that express high levels of G-CSF have the potential to diminish or abrogate the efficacy of breast cancer ATCVs. Fortunately, this study demonstrates that genetic ablation of immunosuppressive cytokines, such as G-CSF, can enhance the immunogenicity of breast cancer cell-based vaccines. Strategies that combine inhibition of immunosuppressive factors with immune stimulatory co-formulations already under development may help ATCVs reach their full potential.Electronic supplementary materialThe online version of this article (10.1186/s13058-018-1054-3) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Tumor-derived granulocyte colony-stimulating factor diminishes efficacy of breast tumor cell vaccines

et al. 2018

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“…Furthermore, the allogeneic cell lines have the capability to contain one/two tumor-associated Ags for a specific tumor with a low complexity of tumor's Ag, inducing unfavorable selective pressure and promote tumor escape. 57 …”

Section: Vaccine Design For Breast Cancermentioning

confidence: 99%

Breast cancer vaccination comes to age: impacts of bioinformatics

Parvizpour¹,

Razmara²,

Omidi³

2018

Bioimpacts

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Introduction: Breast cancer, as one of the major causes of cancer death among women, is the central focus of this study. The recent advances in the development and application of computational tools and bioinformatics in the field of immunotherapy of malignancies such as breast cancer have emerged the new dominion of immunoinformatics, and therefore, next generation of immunomedicines . Methods: Having reviewed the most recent works on the applications of computational tools, we provide comprehensive insights into the breast cancer incidence and its leading causes as well as immunotherapy approaches and the future trends. Furthermore, we discuss the impacts of bioinformatics on different stages of vaccine design for the breast cancer, which can be used to produce much more efficient vaccines through a rationalized time- and cost-effective in silico approaches prior to conducting costly experiments. Results: The tools can be significantly used for designing the immune system-modulating drugs and vaccines based on in silico approaches prior to in vitro and in vivo experimental evaluations. Application of immunoinformatics in the cancer immunotherapy has shown its success in the pre-clinical models. This success returns back to the impacts of several powerful computational approaches developed during the last decade. Conclusion: Despite the invention of a number of vaccines for the cancer immunotherapy, more computational and clinical trials are required to design much more efficient vaccines against various malignancies, including breast cancer.

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“…Treatment with cell-free vaccines consists on direct inoculation of single or multi antigens, later presented to host antigen-presenting cell (APC) that, upon such stimulation, migrate to lymph nodes where they boost immune response. In this group are included a peptide, multipeptide, and heat-shock protein (HSP) vaccines, whose applicability has already been developed for GBM [11][12][13].…”

Section: Cell-free Vaccinesmentioning

confidence: 99%

“…• Bypass the endogenous DC dysfunction in cancer patients; [43] • Cross-presentation of exogenous antigens by DC; [44] • Great ability of DC to prime T cells to attack the tumor; [44] • AFTV provide the entire spectrum of TAAs with no need to select the most proper antigen to target the tumor; [45] • Safe, multivalent and patient-specific [12] • High production costs; [42] • Quality concerns due to the manufacture highly variable; [12,42] • Poor immunogenicity of the tumor cell themselves; [12] • Most of them are restricted to patients with a resectable tumor; [42,46] • Some failure rate associated with culture of autologous tumor cells [46] MHC: major histocompatibility complex; APC: antigen-presenting cell; DC: dendritic cell; TAA: tumor-associated antigens; AFTV: autologous formalin-fixed tumor vaccine.…”

Section: Strategy Advantages Disadvantagesmentioning

confidence: 99%

Impact of Immunotherapy in the Treatment of Glioblastoma

Silva¹,

Miranda²,

Sousa³

et al. 2018

Biopharmaceuticals

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Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor. Despite the efforts developed in the respective treatment, consisting of maximal surgical resection followed by adjuvant radiotherapy and chemotherapy, the prognosis remains very poor. This may be partly related to the resistance of GBM cells and their infiltrative and invasive nature into the surrounding brain tissue. Therefore, newer and challenging alternative approaches for the treatment have emerged, including immunotherapy. This anticancer therapy, based on the stimulation of the host's immune system, has been currently investigated and several advances in the clinical trial stage have already been reached. Immunotherapeutic strategies comprise a set of modalities, including vaccines (cell-free and cell-based), chimeric antigen receptor (CAR) T-cell therapy, immune checkpoint inhibitors, monoclonal antibodies (mAbs), and oncolytic viruses (OVs). In this chapter, we will review the principal concepts and the recent progress in immunotherapy for GBM.

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Current status of autologous breast tumor cell-based vaccines

Cited by 22 publications

References 41 publications

Tumor-derived granulocyte colony-stimulating factor diminishes efficacy of breast tumor cell vaccines

Tumor-derived granulocyte colony-stimulating factor diminishes efficacy of breast tumor cell vaccines

Breast cancer vaccination comes to age: impacts of bioinformatics

Impact of Immunotherapy in the Treatment of Glioblastoma

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