Background Aims: Dendritic cells (DCs) are professional antigen-presenting cells of the mammalian immune system. Ex vivo differentiated DCs represent a unique Advanced Therapy Medicinal Product (ATMP), used in several clinical trials as personalized cancer immunotherapy. The therapy's reliability depends on its capacity to produce high-quality mature DCs (mDCs) in compliance with Good Manufacturing Practices.
View Article and Find Full Text PDFFor advanced therapy medicinal products, the development and validation of potency assays are required, in accordance with international guidelines, to characterise the product and obtain reliable and consistent data. Our purpose was to validate the killing assay for the evaluation of autologous anti-CD19 chimeric antigen receptor (CAR) T potency. We used CD4 + and CD8 + lymphocytes or anti-CD19 CAR-T cells as effector cells and REH (CD19 +) or MOLM-13 (CD19 -) cell lines as target cells.
View Article and Find Full Text PDFItal J Dermatol Venerol
December 2023
Colorectal cancer (CRC) is the third most frequent cancer and the second leading cause of cancer-related deaths in Europe. About 5% of metastatic CRC (mCRC) are characterized by high microsatellite instability (MSI) due to a deficient DNA mismatch repair (dMMR), and this condition has been related to a high sensitivity to immunotherapy, in particular to the Immune Checkpoint Inhibitors (ICIs). In fact, in MSI-H or dMMR mCRC, treatment with ICIs induced remarkable response rates and prolonged survival.
View Article and Find Full Text PDFPurpose: The aims of our retrospective study investigated the role of immune system in glioblastoma (GBM), which is the most aggressive primary brain tumor in adults characterized by a poor prognosis. The recurrence rate remains high, probably due to "immune-desert" tumor microenvironment (TME) making GBM hidden from the anti-tumoral immune clearance. Considering this, we aimed to create a panel of prognostic markers from blood and tumor tissue correlating with overall survival (OS) and progression-free survival (PFS).
View Article and Find Full Text PDFCancer immunotherapy embraces many current, promising therapeutic approaches to eradicate tumors by activating host antitumor activity [...
View Article and Find Full Text PDFBreast cancer represents one of the most common tumor histologies. To date, based on the specific histotype, different therapeutic strategies, including immunotherapies, capable of prolonging survival are used. More recently, the astonishing results that were obtained from CAR-T cell therapy in haematological neoplasms led to the application of this new therapeutic strategy in solid tumors as well.
View Article and Find Full Text PDFAdvanced therapy medical products (ATMPs) are rapidly growing as innovative medicines for the treatment of several diseases. Hence, the role of quality analytical tests to ensure consistent product safety and quality has become highly relevant. Several clinical trials involving dendritic cell (DC)-based vaccines for cancer treatment are ongoing at our institute.
View Article and Find Full Text PDFBackground: To evaluate the capability of basal and one-month differed white blood cells (WBC), neutrophil, lymphocyte and platelet values and their ratios (neutrophils-to-lymphocytes ratio, NLR, and platelets-to-lymphocytes ratio, PLR) in predicting the response to immune checkpoint inhibitors (ICI) in metastatic melanoma (MM).
Methods: We performed a retrospective study of 272 BRAF wild-type MM patients treated with first line ICI. Bivariable analysis was used to correlate patient/tumor characteristics with clinical outcomes.
Background: The long-term increase in survival from cutaneous malignant melanoma (CMM) is generally attributed to the decreasing trend in tumour thickness, the single most important prognostic factor.
Objectives: To determine the relative contribution of decreased tumour thickness to the favourable trend in survival from CMM in Italy.
Methods: Eleven local cancer registries covering a population of 8 056 608 (13.
High-dose interleukin-2 (HD IL-2) has curative potential in metastatic melanoma (MM) and renal cell carcinoma (RCC). Radiotherapy (RT) kills cancer cells and induces immunomodulatory effects. Prospective trials exploring clinical and immunological properties of combined RT/HD IL-2 are still needed.
View Article and Find Full Text PDFTherap Adv Gastroenterol
February 2021
It is debated whether the NRAS-mutant melanoma is more aggressive than NRAS wildtype. It is equally controversial whether NRAS-mutant metastatic melanoma (MM) is more responsive to checkpoint inhibitor immunotherapy (CII). 331 patients treated with CII as first-line were retrospectively recruited: 162 NRAS-mutant/BRAF wild-type (mut/wt) and 169 wt/wt.
View Article and Find Full Text PDFBackground: Advanced age is associated with comorbidities and immune system impairment, which may influence the efficacy and tolerability of immune checkpoint inhibitors. There is evidence that anti-PD1 antibodies in advanced melanoma are equally effective in patients >65 years. However, data on patients >75 years are lacking as co-morbidities and logistics often exclude them from clinical trials.
View Article and Find Full Text PDFGOLFIG is a chemo-immunotherapy regimen established in preclinical models that combines gemcitabine + FOLFOX (fluoropyrimidine backbone coupled to oxaliplatin) poly-chemotherapy with low-dose s. c. recombinant interleukin-2 (rIL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF).
View Article and Find Full Text PDFDendritic cell (DC)-based vaccination effectively induces anti-tumor immunity, although in the majority of cases this does not translate into a durable clinical response. However, DC vaccination is characterized by a robust safety profile, making this treatment a potential candidate for effective combination cancer immunotherapy. To explore this possibility, understanding changes occurring in the tumor microenvironment (TME) upon DC vaccination is required.
View Article and Find Full Text PDFContrast-enhanced computed tomography (CECT) is an indispensable tool in the management of cancer patients. However, this procedure can be complicated by the development of acute adverse reactions (ARs) to iodinated contrast media (ICM). On the basis of the hypothesis that cancer immunotherapy, in particular with immune checkpoint inhibitors, increases the incidence of allergic-like immediate ARs to ICM with respect to "standard" cancer chemotherapy/targeted therapy (CHT) we retrospectively evaluated the incidence of CECT-related immediate ARs in cancer patients undergoing cancer treatments.
View Article and Find Full Text PDFAim: This observational study investigates the effectiveness and safety of dabrafenib/trametinib combination in patients with metastatic melanoma.
Patients & Methods: Seventy-six patients treated with dabrafenib/trametinib (150 mg twice daily/2 mg once daily) were included.
Results: Median progression-free survival was 9 months (95% CI: 7-11) and median overall survival was 14 months (11-16); disease control rate was 72%.
Background: Dendritic cells (DCs) are the most efficient antigen-presenting cells and act at the center of the immune system owing to their ability to control both immune tolerance and immunity. In cancer immunotherapy, DCs play a key role in the regulation of the immune response against tumors and can be generated ex vivo with different cytokine cocktails.
Methods: We evaluated the feasibility of dinoprostone (PGE) replacement with the molecular analog sulprostone, in our good manufacturing practice (GMP) protocol for the generation of DC-based cancer vaccine.
Although immunomodulating antibodies are highly effective in metastatic melanoma, their toxicity, related to the activation of T lymphocytes, can be severe. Anticancer vaccines promote a fairly specific response and are very well tolerated, but their effectiveness has yet to be demonstrated. We have been treating patients with advanced melanoma with an autologous dendritic cell vaccine since 2001; to better characterize the safety and efficacy of our product, we designed a retrospective study on all of our patients treated with the vaccine to date.
View Article and Find Full Text PDFBackground: Tumor cells killed by radiation therapy (RT) are a potentially good source of antigens for dendritic cell (DC) uptake and presentation to T-cells. RT upregulates cell death receptors such as Fas/CD95 and MHC-I, induces the expression of co-stimulatory molecules on tumor cells, and promotes production of pro-inflammatory cytokines. High-dose interleukin-2 (HD-IL-2) bolus has been shown to obtain objective response rates ranging from 15% to 17% in patients with metastatic melanoma or renal cell carcinoma (RCC), with 6% to 8% of cases experiencing a durable complete response.
View Article and Find Full Text PDFBackground: Vaccination with dendritic cells (DC) loaded with tumor antigens elicits tumor-specific immune responses capable of killing cancer cells without inducing meaningful side-effects. Patients with advanced melanoma enrolled onto our phase II clinical studies have been treated with autologous DC loaded with autologous tumor lysate/homogenate matured with a cytokine cocktail, showing a clinical benefit (PR + SD) in 55.5% of evaluable cases to date.
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