EGFR-specific CAR-T cells trigger cell lysis in EGFR-positive TNBC.

In this study, we generated two types of EGFR-specific CAR-modified T cells using lentiviral vectors with DNA sequences encoding the scFv regions of two anti-EGFR antibodies. The cytotoxic and antitumor effects of these CAR-modified T cells were examined in cytokine release and cytotoxicity assays in vitro and in tumor growth assays in TNBC cell line- and patient-derived xenograft mouse models. Both types of EGFR-specific CAR-T cells were activated by high-EGFR-expressing TNBC cells and specifically triggered TNBC cell lysis in vitro. Additionally, the CAR-T cells inhibited growth of cell-line- and patient-derived xenograft TNBC tumors in mice. These results suggest that EGFR-specific CAR-T cells might be a promising therapeutic strategy in patients with high-EGFR-expressing TNBC. PMID: 31804974 [PubMed - as supplied by publisher]
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research

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AbstractClinical progress in the field of HER2-positive breast cancer therapy has been dramatically improved by understanding of the immune regulatory mechanisms of tumor microenvironment. Passive immunotherapy utilizing recombinant monoclonal antibodies (mAbs), particularly trastuzumab and pertuzumab has proved to be an effective strategy in HER2-positive breast cancer treatment. However, resistance to mAb therapy and relapse of disease are still considered important challenges in clinical practice. There are increasing reports on the induction of cellular and humoral immune responses in HER2-positive breast cancer patien...
Source: Archivum Immunologiae et Therapiae Experimentalis - Category: Allergy & Immunology Source Type: research
In conclusion, sensory nerve fibers sensitive to capsaicin have important roles in defense against metastatic breast carcinoma; hence, controlled activation of these neural pathways might be effective in cancer therapy. Specifically, activation of sensory fibers of left vagus nerve using a perineuronal stimulation may inhibit metastasis of breast carcinoma. Likewise, pharmacological modulators of TRPV1 channels may induce anti-tumoral immune response. Exact players of this newly explored defense system are, however, only partly validated, and further studies are required.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Publication date: Available online 24 December 2019Source: Seminars in Cancer BiologyAuthor(s): Constantin N. Baxevanis, Sotirios P. Fortis, Sonia A. PerezAbstractCancer evolution is a complex process influenced by genetic factors and extracellular stimuli that trigger signaling pathways to coordinate the continuous and dynamic interaction between tumor cells and the elements of the immune system. For over 20 years now, the immune mechanisms controlling cancer progression have been the focus of intensive research. It is well established that the immune system conveys protective antitumor immunity by destroying immunogenic ...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
AbstractCurrent therapeutic approaches in malignancy are often based on combination therapies, reflecting present understanding of the way different players act together in cancer. The cooperative activity of several elements can potentiate the pro-metastatic functions of the cancer cells and of the tumor microenvironment (TME), together leading to a more aggressive disease phenotype. The design of improved therapeutic modalities requires better identification of networks that act at specific cancer-related settings, and of the molecular mechanisms involved. Such studies will indicate if therapies that co-target several fa...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology 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
Yicheng Ni Cancer remains a major cause of death globally. Given its relapsing and fatal features, curing cancer seems to be something hardly possible for the majority of patients. In view of the development in cancer therapies, this article summarizes currently available cancer therapeutics and cure potential by cancer type and stage at diagnosis, based on literature and database reviews. Currently common cancer therapeutics include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, treatment with curative intent by these methods are mainly eligible for patients with localized diseas...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
AbstractPARP (poly(ADP-ribose) polymerase) inhibitors represent a novel class of anti-cancer therapy; they take advantage of synthetic lethality and induce cell death by exploiting a defect in DNA repair. This class of medication was initially evaluated in patients with BRCA-associated tumors, but efficacy was also demonstrated in other populations. Since 2014, four PARP inhibitors have been approved in various indications: olaparib, niraparib, and rucaparib in high-grade serous ovarian cancer, and olaparib and talazoparib in metastatic breast cancer. The exact indications and study populations vary slightly between the di...
Source: Targeted Oncology - Category: Cancer & Oncology Source Type: research
AbstractDespite the efforts that have been made in the field of breast cancer therapy, it is a leading cause of cancer death in women and a major health problem. The current treatments combine several strategies (surgery, radiotherapy, immunotherapy, hormone therapy, and chemotherapy) depending on cancer subtype and tumour stage. The use of chemotherapy is required in certain circumstances, like before or after surgery or in advanced stages of the disease. Chemotherapeutic regimens that include anthracyclines (e.g. doxorubicin), taxanes (e.g. paclitaxel), 5-fluorouracil and/or cyclophosphamide show, in general, a high toxi...
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
Conclusions: Mortalin promotes cell proliferation, metastasis, angiogenesis, downregulate apoptotic signaling. Thus, mortalin is a potential therapeutic target for cancer immunotherapy. The novel SMRwt peptides antagonize the functions of mortalin, blocking tumor extracellular vesicle release and extracellular vesicle-mediated release of complement. This leads to decreases in breast cancer cell metastasis and allows standard treatment of these late stage tumor cells, thus having important clinical implications for late stage breast cancer chemotherapy. These findings support further investigation into the therapeutic value...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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