Tumor heterogeneity as a rationale for a multi-epitope approach in an autologous renal cell cancer tumor vaccine

Wittke, Stefan; Baxmann, Susann; Fahlenkamp, D.; Kießig, S.T.

doi:10.2147/ott.s92182

Cited by 11 publications

(6 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adjuvant breast cancer vaccines are of interest due to their potential to educate a patient’s immune system to recognize and eliminate occult tumor cells before a recurrence can develop. In particular, autologous tumor cell vaccines (ATCVs) comprise a promising class of vaccines capable of inducing personalized, polyclonal anti-tumor immune responses [ 5 – 14 ]. Patient/tumor-specific polyclonal immune responses are especially relevant for breast cancer with high intra-patient and inter-patient molecular heterogeneity that facilitates resistance to targeted therapies [ 15 – 19 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

View full text Add to dashboard Cite

show abstract

“…A selective isolation of tumor cells from other cellular components should be considered to limit pre-analytic bias during the analytic process. Several approaches have been used to deal with the problem, including micro-dissection profiling, and laser capture microdissection (LCM) [55–57]. The approach of micro-dissecting tumor tissue uses microscopy to identify tumor areas, and provides samples from selective areas of the tumor.…”

Section: Challenges and Opportunitiesmentioning

confidence: 99%

Challenges and opportunities in the proteomic characterization of clear cell renal cell carcinoma (ccRCC): A critical step towards the personalized care of renal cancers

Pavlovich

Zhang

et al. 2019

Seminars in Cancer Biology

View full text Add to dashboard Cite

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, comprising approximately 75% of all kidney tumors. Recent the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) studies have significantly advanced the molecular characterization of RCC and facilitated the development of targeted therapies. Such advances have improved the median survival of patients with advanced disease from less than 10 months prior to 2004 to 30 months by 2011. However, approximately 30% of localized ccRCC patients will nevertheless develop recurrence or metastasis after surgical resection of their tumor. Therefore, it is critical to further analyze potential tumor-associated proteins and their profiles during disease progression. Over the past decade, tremendous effort has been focused on the study of molecular pathways, including genomics, transcriptomics, and proteomics in order to identify potential molecular biomarkers, as well as to facilitate early detection, monitor tumor progression and uncover potentially therapeutic targets. In this review, we focus on recent advances in the proteomic analysis of ccRCC, current strategies and challenges, and perspectives in the field. This insight will highlight the discovery of tumor-associated proteins, and their potential clinical impact on personalized precision-based care in ccRCC.

show abstract

“…Principally, autologous tumor cell lysate vaccine active APCs, such as dendritic cells, which stimulate a cytotoxic T lymphocyte response toward tumor-associated antigens, leading to tumor cell destruction [26][27][28]. Adjuvant treatment with autologous vaccination Reniale (Liponova AG, Hannover, Germany) improved OS in pT3 RCC patients (10-year OS rates: 53.6% in vaccine group versus 36.2% in control group; p = 0.022) in a phase III study [29].…”

Section: Autologous Tumor Cell Lysate (Reniale)mentioning

confidence: 99%

Immunotherapy for Renal Cell Carcinoma

Qu¹,

Wu²,

He³

et al. 2020

Evolving Trends in Kidney Cancer

View full text Add to dashboard Cite

Despite the rapid development of therapeutic modalities for advanced or metastatic renal cell carcinoma (mRCC) over the past decade to include traditional immunotherapy, such as high-dose interleukin-2 and interferon-α, as well as a number of targeted antiangiogenic therapies, mRCC continues to be associated with poor prognosis. Currently, immunotherapy has seen tremendous development in the form of immune checkpoint inhibition and vaccines at a dizzying pace, which are being studied in mRCC and are showing promise as important steps in the management of this disease. With so many drugs available to clinicians and patients, properly integrating immunotherapy especially immune checkpoint blockade (ICB) into the treatment paradigm is challenging. Emerging research with additional ICB agents and novel combination strategies is likely to further impact clinical decision-making. The further development of biomarkers for predicting a response is required to achieve optimal efficacy with these therapeutic interventions. This chapter summarizes the current landscape of standard and emerging immune therapeutics and other modalities for mRCC.

show abstract

Tumor heterogeneity as a rationale for a multi-epitope approach in an autologous renal cell cancer tumor vaccine

Cited by 11 publications

References 35 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

Challenges and opportunities in the proteomic characterization of clear cell renal cell carcinoma (ccRCC): A critical step towards the personalized care of renal cancers

Immunotherapy for Renal Cell Carcinoma

Contact Info

Product

Resources

About