Search results for "immunotherapy"

Inhibitors of apoptosis confer resistance to tumour suppression by adoptively transplanted cytotoxic T-lymphocytes in vitro and in vivo

2005

Deregulation of apoptosis signalling is commonly found in cancer and results in resistance to cytotoxic therapies. Immunotherapy is a promising strategy to eliminate resistant cancer cells. The transfer of T-lymphocytes during allogeneic stem cell transplantation is clinically explored to induce a 'graft-versus-tumor' effect (GvT). Cytotoxic T-lymphocytes (CTL), which are major effectors of GvT, eliminate cancer cells by inducing apoptosis via multiple parallel pathways. Here, we study in vitro and in vivo the susceptibility of murine cancer cells engineered to express single antiapoptotic genes to CTL-mediated cytotoxicity. Interestingly, we find that single inhibitors of caspase activatio…

Toll-like Receptor 2 and 4 in Cancer Immunotherapy: Is Nitric Oxide a Mediator?

2010

In vivo manipulation of Vgamma9Vdelta2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients.

2010

The potent anti-tumour activities of gamma delta T cells have prompted the development of protocols in which gamma delta-agonists are administered to cancer patients. Encouraging results from small Phase I trials have fuelled efforts to characterize more clearly the application of this approach to unmet clinical needs such as metastatic carcinoma. To examine this approach in breast cancer, a Phase I trial was conducted in which zoledronate, a V gamma 9V delta 2 T cell agonist, plus low-dose interleukin (IL)-2 were administered to 10 therapeutically terminal, advanced metastatic breast cancer patients. Treatment was well tolerated and promoted the effector maturation of V gamma 9V delta 2 T …

IL-4 depletion enhances host resistance and passive IgA protection against tuberculosis infection in BALB/c mice.

2007

The influence of Th2 cytokines in tuberculosis has been a matter of dispute. Here we report that IL-4 has a profound regulatory effect on the infection of BALB/c mice with Mycobacterium tuberculosis. Depletion of IL-4 with a neutralizing mAb caused only evanescent reduction of lung infection, but when combined with i.n. inoculations of IgA anti-mycobacterial alpha-crystallin mAb and mouse rIFN-gamma, we observed a 40-fold reduction of the bacterial counts in the lungs at 3 wks following i.n. infection (p<0.001). In genetically deficient IL-4-/- BALB/c mice, infection in both lung and spleen was substantially reduced for up to 8 wks without further treatment. Reconstitution of IL-4-/- mice w…

Fasting renders immunotherapy effective against low-immunogenic breast cancer while reducing side effects

2022

Immunotherapy is improving the prognosis and survival of cancer patients, but despite encouraging out-comes in different cancers, the majority of tumors are resistant to it, and the immunotherapy combinations are often accompanied by severe side effects. Here, we show that a periodic fasting-mimicking diet (FMD) can act on the tumor microenvironment and increase the efficacy of immunotherapy (anti-PD-L1 and anti-OX40) against the poorly immunogenic triple-negative breast tumors (TNBCs) by expanding early exhausted effector T cells, switching the cancer metabolism from glycolytic to respiratory, and reducing collagen depo-sition. Furthermore, FMD reduces the occurrence of immune-related adve…

Clinico-Pathological Features Influencing the Prognostic Role of Body Mass Index in Patients With Advanced Renal Cell Carcinoma Treated by Immuno-Onc…

2023

Background: Obesity has been associated with improved response to immunotherapy in cancer patients. We investigated the role of body mass index (BMI) in patients from the ARON-1 study (NCT05287464) treated by dual immuno-oncology agents (IO+IO) or a combination of immuno-oncology drug and a tyrosine kinase inhibitors (TKI) as first-line therapy for metastatic renal cell carcinoma (mRCC). Patients and methods: Medical records of patients with documented mRCC treated by immuno-oncology combinations were reviewed at 47 institutions from 16 countries. Patients were assessed for overall survival (OS), progression-free survival (OS), and overall clinical benefit (OCB), defined as the sum of the r…

2019

Glycoprotein A repetition predominant (GARP), a specific surface molecule of activated regulatory T cells, has been demonstrated to significantly contribute to tolerance in humans by induction of peripheral Treg and regulatory M2-macrophages and by inhibition of (tumorantigen-specific) T effector cells. Previous work identified GARP on Treg, and also GARP on the surface of several malignant tumors, as well as in a soluble form being shedded from their surface, contributing to tumor immune escape. Preliminary results also showed GARP expression on brain metastases of malignant melanoma. On the basis of these findings, we investigated whether GARP is also expressed on primary brain tumors. We…

Not just for tumor targeting: unmet medical needs and opportunities for nanomedicine.

2015

During the last 3 decades, nanomedicines have provided novel opportunities to improve the delivery of chemotherapeutics in cancer therapy effectively. However, many principles learnt from there have the potential to be transferred to other diseases. This perspective article, on the one hand, critically reflects the limitations of nanomedicines in tumor therapy and, on the other hand, provides alternative examples of nanomedicinal applications in immunotherapy, noninvasive drug deliveries across epithelial barriers and strategies to combat intra- and extra-cellular bacterial infections. Looking ahead, access to highly complex nanoparticular delivery vehicles given nowadays may allow further…

Tumor-infiltrating lymphocytes and breast cancer: Beyond the prognostic and predictive utility

2017

The importance of the immune system as a potent anti-tumor defense has been consolidated in recent times, and novel immune-related therapies are today demonstrating a strong clinical benefit in the setting of several solid neoplasms. Tumor-infiltrating lymphocytes reflect the attempt of the host to eradicate malignancies, and during the last decades, they have been shown to possess an interesting prognostic utility for breast cancer, especially in case of HER2 positive and triple-negative molecular subtypes. In parallel, the clinical evaluation of tumor-infiltrating lymphocytes has been shown to effectively predict treatment outcomes in both neoadjuvant and adjuvant settings. Currently, tu…

Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells.

2006

AbstractAdoptive transfer of dendritic cells (DCs) transfected with in vitro–transcribed, RNA-encoding, tumor-associated antigens has recently entered clinical testing as a promising approach for cancer immunotherapy. However, pharmacokinetic exploration of RNA as a potential drug compound and a key aspect of clinical development is still pending. While investigating the impact of different structural modifications of RNA molecules on the kinetics of the encoded protein in DCs, we identified components located 3′ of the coding region that contributed to a higher transcript stability and translational efficiency. With the use of quantitative reverse transcription–polymerase chain reaction (R…