Emerging CAR-T Cell Therapy for the Treatment of Triple-Negative Breast Cancer

Dees, Sundee; Ganesan, Rajkumar; Singh, Sanjaya; Grewal, Iqbal S.

doi:10.1158/1535-7163.mct-20-0385

Cited by 69 publications

(81 citation statements)

References 114 publications

(93 reference statements)

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“…Cell surface antigens, including RTKs (e.g., AXL, EGFR, MET, ROR, etc. ), which are overexpressed in TNBCs, are promising targets for CAR-T cell therapy [ 597 ]. Since in vitro and in vivo studies have demonstrated the efficacy of CAR-T cell therapy against TNBC cells, combination approaches may further expand the therapeutic opportunities in the future.…”

Section: Combination Strategy For Overcoming Egfri Resistance In Tnbcmentioning

confidence: 99%

Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer

You

Cho

et al. 2021

Pharmaceuticals

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Triple-negative breast cancer (TNBC) is a subset of breast cancer with aggressive characteristics and few therapeutic options. The lack of an appropriate therapeutic target is a challenging issue in treating TNBC. Although a high level expression of epidermal growth factor receptor (EGFR) has been associated with a poor prognosis among patients with TNBC, targeted anti-EGFR therapies have demonstrated limited efficacy for TNBC treatment in both clinical and preclinical settings. However, with the advantage of a number of clinically approved EGFR inhibitors (EGFRis), combination strategies have been explored as a promising approach to overcome the intrinsic resistance of TNBC to EGFRis. In this review, we analyzed the literature on the combination of EGFRis with other molecularly targeted therapeutics or conventional chemotherapeutics to understand the current knowledge and to provide potential therapeutic options for TNBC treatment.

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Section: Combination Strategy For Overcoming Egfri Resistance In Tnbcmentioning

confidence: 99%

Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer

You

Cho

et al. 2021

Pharmaceuticals

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“…FDA-approved therapies that target the DNA damage repair mechanism of TNBC, such as PARP inhibitors, have shown minimal clinical benefit yet [ 48 , 49 ]. A recent clinical precedent has been established by FDA approval for two TNBC immunotherapies, including an antibody-drug conjugate and an anti-PD-L1 agent [ 50 , 51 ]. The discovery of six molecular subtypes of TNBC, one of which is an immunomodulatory subtype, further accelerated the development of immunotherapeutic strategies for this disease indication [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

“…The discovery of six molecular subtypes of TNBC, one of which is an immunomodulatory subtype, further accelerated the development of immunotherapeutic strategies for this disease indication [ 52 ]. In addition, chimeric antigen receptor (CAR)-T cell therapy, a type of adoptive cell therapy that combines the antigen specificity of an antibody with the effector function of T cells, has emerged as a promising immunotherapy strategy to improve the survival rate of TNBC patients [ 50 , 53 ]. In our study, in the triple-negative subtype, CD8+ T cells were significantly lower in BCBM than in primary BC.…”

Section: Discussionmentioning

confidence: 99%

Evolution of the Tumor Microenvironment toward Immune-Suppressive Seclusion during Brain Metastasis of Breast Cancer: Implications for Targeted Therapy

Noh

Kim

et al. 2021

Cancers

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Breast cancer (BC) is the second most common solid malignant tumor that metastasizes to the brain. Despite emerging therapies such as immunotherapy, whether the tumor microenvironment (TME) in breast cancer brain metastasis (BCBM) has potential as a target of new treatments is unclear. Expression profiling of 770 genes in 12 pairs of primary BC and matched brain metastasis (BM) samples was performed using the NanoString nCounter PanCancer IO360TM Panel. Immune cell profiles were validated by immunohistochemistry (IHC) in samples from 50 patients with BCBM. Pathway analysis revealed that immune-related pathways were downregulated. Immune cell profiling showed that CD8+ T cells and M1 macrophages were significantly decreased, and M2 macrophages were significantly increased, in BM compared to primary BC samples (p = 0.001, p = 0.021 and p = 0.007, respectively). CCL19 and CCL21, the top differentially expressed genes, were decreased significantly in BM compared to primary BC (p < 0.001, both). IHC showed that the CD8+ count was significantly lower (p = 0.027), and the CD163+ and CD206+ counts were higher, in BM than primary BC (p < 0.001, both). A low CD8+ T cell count, low CD86+ M1 macrophage count, and high M2/M1 macrophage ratio were related to unfavorable clinical outcomes. BC exhibits an immunosuppressive characteristic after metastasis to the brain. These findings will facilitate establishment of a treatment strategy for BCBM based on the TME of metastatic cancer.

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“…Despite that, some potential neoantigen targets are being tested in phase II trials. Chimeric CAR-T-cells targeting both antigenic target and other TME cells are also being developed to overcome the immunosuppressive TME [208].…”

Section: Therapies Targeting the Tumor Microenvironmentmentioning

confidence: 99%

Tumor Microenvironment in Breast Cancer—Updates on Therapeutic Implications and Pathologic Assessment

Tsang

Tse

2021

Cancers

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The tumor microenvironment (TME) in breast cancer comprises local factors, cancer cells, immune cells and stromal cells of the local and distant tissues. The interaction between cancer cells and their microenvironment plays important roles in tumor proliferation, propagation and response to therapies. There is increasing research in exploring and manipulating the non-cancerous components of the TME for breast cancer treatment. As the TME is now increasingly recognized as a treatment target, its pathologic assessment has become a critical component of breast cancer management. The latest WHO classification of tumors of the breast listed stromal response pattern/fibrotic focus as a prognostic factor and includes recommendations on the assessment of tumor infiltrating lymphocytes and PD-1/PD-L1 expression, with therapeutic implications. This review dissects the TME of breast cancer, describes pathologic assessment relevant for prognostication and treatment decision, and details therapeutic options that interacts with and/or exploits the TME in breast cancer.

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Emerging CAR-T Cell Therapy for the Treatment of Triple-Negative Breast Cancer

Abstract: Financial support: All authors are paid employees of the Janssen Pharmaceuticals, Johnsons & Johnson Group of companies and receiving salary and other compensation.

Cited by 69 publications

References 114 publications

Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer

Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer

Evolution of the Tumor Microenvironment toward Immune-Suppressive Seclusion during Brain Metastasis of Breast Cancer: Implications for Targeted Therapy

Tumor Microenvironment in Breast Cancer—Updates on Therapeutic Implications and Pathologic Assessment

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