Publications by authors named "Noor Bakker"

Article Synopsis
  • Immune checkpoint inhibition (ICI) combined with chemotherapy is the standard treatment for stage II-III triple-negative breast cancer, but the effectiveness of ICI alone remains unclear.
  • The adaptive BELLINI trial found that short-term ICI treatments led to immune activation in a significant portion of patients, correlating immune response with tumor-infiltrating lymphocytes.
  • A new cohort is being studied with patients who have high levels of these lymphocytes; early results show a notable rate of major and complete pathological responses post-treatment, suggesting that neoadjuvant ICI could be a promising approach without chemotherapy.
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Article Synopsis
  • Immune checkpoint blockade (ICB) is gaining traction in treating advanced cancer patients, but its effects on the immune system and cancer spread in neoadjuvant settings are not fully understood.
  • Tumors can promote the expansion of regulatory T cells (T), which may inhibit ICB effectiveness and contribute to cancer progression.
  • Research shows that depleting T cells during neoadjuvant ICB boosts the immune response, increases survival related to metastasis, and shows that targeting T cells might improve outcomes without necessarily shrinking the primary tumor.
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Invasive lobular breast cancer (ILC) is the second most common histological breast cancer subtype, but ILC-specific trials are lacking. Translational research revealed an immune-related ILC subset, and in mouse ILC models, synergy between immune checkpoint blockade and platinum was observed. In the phase II GELATO trial ( NCT03147040 ), patients with metastatic ILC were treated with weekly carboplatin (area under the curve 1.

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Immune checkpoint blockade (ICB) has heralded a new era in cancer therapy. Research into the mechanisms underlying response to ICB has predominantly focused on T cells; however, effective immune responses require tightly regulated crosstalk between innate and adaptive immune cells. Here, we combine unbiased analysis of blood and tumors from metastatic breast cancer patients treated with ICB with mechanistic studies in mouse models of breast cancer.

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Background: Usual vulvar intraepithelial neoplasia (uVIN) is a premalignancy caused by persistent infection with high-risk types of human papillomavirus (HPV), mainly type 16. Even though different treatment modalities are available (eg, surgical excision, laser evaporation or topical application of imiquimod), these treatments can be mutilating, patients often have recurrences and 2%-8% of patients develop vulvar carcinoma. Therefore, immunotherapeutic strategies targeting the pivotal oncogenic HPV proteins E6 and E7 are being explored to repress carcinogenesis.

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Unlabelled: Treatment of metastatic melanoma with autologous tumor infiltrating lymphocytes (TILs) is currently applied in several centers. Robust and remarkably consistent overall response rates, of around 50% of treated patients, have been observed across hospitals, including a substantial fraction of durable, complete responses.

Purpose: Execute a phase I/II feasibility study with TIL therapy in metastatic melanoma at the Netherlands Cancer Institute, with the goal to assess feasibility and potential value of a randomized phase III trial.

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The efficacy of programmed cell death protein 1 (PD-1) blockade in metastatic triple-negative breast cancer (TNBC) is low, highlighting a need for strategies that render the tumor microenvironment more sensitive to PD-1 blockade. Preclinical research has suggested immunomodulatory properties for chemotherapy and irradiation. In the first stage of this adaptive, non-comparative phase 2 trial, 67 patients with metastatic TNBC were randomized to nivolumab (1) without induction or with 2-week low-dose induction, or with (2) irradiation (3 × 8 Gy), (3) cyclophosphamide, (4) cisplatin or (5) doxorubicin, all followed by nivolumab.

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Cancer cells can evade immune surveillance through the expression of inhibitory ligands that bind their cognate receptors on immune effector cells. Expression of programmed death ligand 1 in tumor microenvironments is a major immune checkpoint for tumor-specific T cell responses as it binds to programmed cell death protein-1 on activated and dysfunctional T cells. The activity of myeloid cells such as macrophages and neutrophils is likewise regulated by a balance between stimulatory and inhibitory signals.

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Article Synopsis
  • There has been increasing demand for small batches of clinical-grade plasmid DNA, prompting the creation of a scaled-down Good Manufacturing Practices (GMP) production method suitable for producing 1-4 mg batches.
  • The new method utilizes simple, disposable materials, making it easy to implement and streamline the production process, with successful production demonstrated for two different plasmids.
  • Quality control tests confirmed the method's effectiveness, revealing that the final formulation remains stable for at least two years and is intended for use in a phase I/II clinical trial for treating Age Related Macular Degeneration.
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