Author's view: radiation and immunotherapy as systemic therapy for solid tumors.
Ontology highlight
ABSTRACT:
SUBMITTER: Seyedin SN
PROVIDER: S-EPMC4404906 | biostudies-other | 2015 Jan
REPOSITORIES: biostudies-other
Similar Datasets
Project description:With the recent success of checkpoint inhibitors and other immunomodulating agents, there has been renewed interest in the combination of such agents with radiation. The biologic premise behind such a strategy is that the tumor-antigen release achieved by localized radiation will promote specific tumor targeting by the adaptive immune system, which can be augmented further by systemic immune-stimulating agents. In this manner, clinicians hope to induce a phenomenon known as the abscopal effect, whereby localized radiation results in immune-mediated tumor regression in disease sites well outside of the radiation field. Herein, we present a comprehensive overview of the early clinical and preclinical evidence behind this approach.
| S-EPMC5367158 | biostudies-literature
Project description:Immunotherapy, particularly immune-checkpoint inhibition, is producing encouraging clinical responses and affecting the way numerous cancers are treated. Yet immune-checkpoint therapy is not effective for many patients, and even those who initially respond can experience relapse, fueling interest in finding new processes or tools to improve the effectiveness of these novel therapeutics. One such tool is radiation. Both preclinical and clinical studies have demonstrated that the systemic effects of immunotherapy can be amplified when it is used in combination with radiation and, conversely, that the immunogenic effects of local irradiation can be amplified and extended to distant sites when used with immunotherapy. We review how stereotactic ablative radiation therapy, a technique specifically indicated for tumors treated with immune-checkpoint inhibitors, can potentiate the effects of immune-checkpoint therapy. We further explore how these novel therapeutics may transform radiation, previously considered a local treatment option, into powerful systemic therapy.
| S-EPMC5812885 | biostudies-literature
Project description:Rational: Tumor immunogenic cell death (ICD), induced by certain chemotherapeutic drugs such as doxorubicin (Dox), is a form of apoptosis potentiating a protective immune response. One of the hallmarks of ICD is the translocation of calreticulin to the cell surface acting as an 'eat me' signal. This manuscript describes the development of a stable nucleic acid-lipid particles (SNALPs) formulation for the simultaneous delivery of ICD inducing drug (Dox) with small interfering RNA (siRNA) knocking down CD47 (siCD47), the dominant 'don't eat me' marker, for synergistic enhancement of ICD. Methods: SNALPs loaded with Dox or siCD47 either mono or combinatory platforms were prepared by ethanol injection method. The proposed systems were characterized for particle size, surface charge, entrapment efficiency and in vitro drug release. The ability of the SNALPs to preserve the siRNA integrity in presence of serum and RNAse were assessed over 48 h. The in vitro cellular uptake and gene silencing of the prepared SNALPs was assessed in CT26 cells. The immunological responses of the SNALPs were defined in vitro in terms of surface calreticulin expression and macrophage-mediated phagocytosis induction. In vivo therapeutic studies were performed in CT26 bearing mice where the therapeutic outcomes were expressed as tumor volume, expression of CD4 and CD8 as well as in vivo silencing. Results: The optimized SNALPs had a particle size 122 ±6 nm and an entrapment efficiency > 65% for both siRNA and Dox with improved serum stability. SNALPs were able to improve siRNA and Dox uptake in CT26 cells with enhanced cytotoxicity. siCD47 SNALPs were able to knockdown CD47 by approximately 70% with no interference from the presence of Dox. The siCD47 and Dox combination SNALPs were able to induce surface calreticulin expression leading to a synergistic effect on macrophage-mediated phagocytosis of treated cells. In a tumor challenge model, 50% of mice receiving siCD47 and Dox containing SNALPs were able to clear the tumor, while the remaining animals showed significantly lower tumor burden as compared to either monotreatment. Conclusion: Therefore, the combination of siCD47 and Dox in a particulate system showed potent anti-tumor activity which merits further investigation in future clinical studies.
| S-EPMC8419059 | biostudies-literature
Project description:Malignant tumors are considered "unresectable" if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120?nm, to form (103)Pd@Au nanoseeds. The therapeutic efficacy of (103)Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of (103)Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.
| S-EPMC4745015 | biostudies-literature
Project description:Adjuvant therapy employing cytotoxic chemotherapy, molecularly targeted agents, immunologic, and hormonal agents has shown a significant impact upon a variety of solid tumors. The principles that guide adjuvant therapy differ among various tumor types and specific modalities, but generally indicate a greater impact of therapy in the postsurgical setting of micrometastatic disease, for which adjuvant therapy is commonly pursued, vs. the setting of gross unresectable disease. This review of adjuvant therapies in current use for five major solid tumors highlights the rationale for current effective adjuvant therapy, and draws comparisons between the adjuvant regimens that have found application in solid tumors.
| S-EPMC8555872 | biostudies-literature
Project description:Recent work with immunotherapy has shown promising results with treatment of several solid malignancies, and there are several reports of good systemic responses with the combination of immunotherapy and radiation therapy (RT), most notably in advanced melanoma. Given the rapid increase in the use of checkpoint blockade as well as anti-tumor vaccines, we review here the preclinical rationale and ongoing clinical work in combining immunotherapy with RT for small cell lung cancer (SCLC) and thymic tumors. While there are several reports of promising results with the combination of immunotherapy and conventional systemic treatment, we focus here on the ongoing clinical studies that combine immunotherapy with RT, and highlight the emerging data for this multimodality approach as well as key preclinical and clinical issues that remain to be addressed. With regards to SCLC, trials exploring to the combination of immunotherapy and RT are already ongoing, but clinical studies for this combination in thymoma are lacking.
| S-EPMC5420531 | biostudies-other
Project description:Metastatic and refractory pediatric solid tumor malignancies continue to have a poor outcome despite the > 80% cure rates appreciated in many pediatric cancers. Targeted immunotherapy is impacting treatment and survival in these aggressive tumors. We review current promising immunotherapeutic approaches in the pediatric oncology solid tumor setting.
| S-EPMC4839383 | biostudies-literature
Project description:Substantial progress has been made in the treatment of pediatric solid tumors over the past 4 decades. However, children with metastatic and or recurrent disease continue to do poorly despite the aggressive multi-modality conventional therapies. The increasing understanding of the tumor biology and the interaction between the tumor and the immune system over the recent years have led to the development of novel immune-based therapies as alternative options for some of these high-risk malignancies. The safety and anti-tumor efficacy of various tumor vaccines and tumor-antigen specific immune cells are currently being investigated for various solid tumors. In early clinical trials, most of these cellular therapies have been well tolerated and have shown promising clinical responses. Although substantial work is being done in this field, the available knowledge for pediatric tumors remains limited. We review the contemporary early phase cell-based immunotherapy efforts for pediatric solid tumors and discuss the rationale and the challenges thereof.
| S-EPMC4629832 | biostudies-literature
Project description:Stereotactic radiosurgery and stereotactic body radiation therapy are two contemporary radiation modalities that can treat tumors in any area of the body using highly focused radiation. Recently, immunotherapy has established itself as a viable and powerful anticancer treatment. In this review we detail the rationale supporting a combination of immunotherapy and stereotactic radiation. Additionally, we discuss the evidence for the immune stimulatory effects of focused radiation and the role that radiation may play in enhancing the systemic treatment effects of immunotherapy.
| S-EPMC4814161 | biostudies-literature
Project description:Treatment recommendations for primary liver malignancies, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are complex and require a multidisciplinary approach. Despite surgical options that are potentially curative, options for nonsurgical candidates include systemic therapy, radiotherapy (RT), transarterial chemoembolization (TACE), and radiofrequency ablation (RFA). Stereotactic Body Radiation Therapy (SBRT) is now in routine use for the treatment of lung cancer, and there is growing evidence supporting its use in liver tumors. SBRT has the advantage of delivering ablative radiation doses in a limited number of fractions while minimizing the risk of radiation-induced liver disease (RILD) through highly conformal treatment plans. It should be considered in a multidisciplinary setting for the management of patients with unresectable, locally advanced primary liver malignancies and limited treatment options. Recently, the combination of immunotherapy with SBRT has been proposed to improve antitumor effects through engaging the immune system. This review aims at shedding light on the novel concept of the combination strategy of immune-radiotherapy in liver tumors by exploring the evidence surrounding the use of SBRT and immunotherapy for the treatment of HCC and CCA.
| S-EPMC6512065 | biostudies-literature