Electrochemotherapy and Other Clinical Applications of Electroporation for the Targeted Therapy of Metastatic Melanoma.
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ABSTRACT:
SUBMITTER: Cucu CI
PROVIDER: S-EPMC8305146 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and study aims Electrochemotherapy is an anticancer treatment that uses electric pulses to facilitate uptake of chemotherapeutic drugs in tumor cells and has proven to have a high local cytotoxic effect with minimal adverse events. Electrochemotherapy has mostly been used in treatment of cutaneous metastases but development of a new endoscopic electrode device has made treatment of colorectal tumors possible. This first-in-man multicenter phase I study investigated safety and efficacy of electrochemotherapy using endoscopic electroporation in patients with colorectal tumors. Patients and methods Seven patients with colorectal tumors who were deemed ineligible for or had declined standard treatment were included. They were treated with bleomycin either intratumorally or intravenously and the electric pulses were delivered through the endoscopic electrode device. Safety and efficacy were assessed clinically and by scans immediately after treatment and adverse events were reported. Response was evaluated up to 6 months after treatment by scans (magnetic resonance imaging or computed tomography) and endoscopic examinations. Results Seven patients aged 62 to 88 years with multiple comorbidities were included and had one or two treatments each. Post-treatment scans showed tumor responses in the treated areas and no damage to surrounding tissues. Only a few grade one adverse events were reported. Three patients had preoperative rectal bleeding, of which two reported cessation of bleeding and one reported decreased bleeding. Conclusion This first-in-man study shows that electrochemotherapy for colorectal tumors using the endoscopic electrode device can induce local tumor response and is safe also for fragile elderly patients with comorbidities.
| S-EPMC6976320 | biostudies-literature
Project description:Despite recent advancements in the diagnosis and treatment of uveal melanoma (UM), its metastatic rate remains high and is accompanied by a highly dismal prognosis, constituting an unmet need for the development of novel adjuvant therapeutic strategies. We established an in vivo chick chorioallantoic membrane (CAM)-based UM xenograft model from UPMD2 and UPMM3 cell lines to examine its feasibility for the improvement of selection of drug candidates. The efficacy of calcium electroporation (CaEP) with 5 or 10 mM calcium chloride (Ca) and electrochemotherapy (ECT) with 1 or 2.5 µg/mL bleomycin in comparison to monotherapy with the tested drug or electroporation (EP) alone was investigated on the generated UM tumors. CaEP and ECT showed a similar reduction of proliferation and melanocytic expansion with a dose-dependent effect for bleomycin, whereas CaEP induced a significant increase of the apoptosis and a reduction of vascularization with varying sensitivity for the two xenograft types. Our in vivo results suggest that CaEP and ECT may facilitate the adequate local tumor control and contribute to the preservation of the bulbus, potentially opening new horizons in the adjuvant treatment of advanced UM.
| S-EPMC10815639 | biostudies-literature
Project description:Electrochemotherapy is a local treatment combining chemotherapy and application of electric pulses to the tumour. Electrochemotherapy with bleomycin and cisplatin has already been found to be effective in controlling local tumour growth in the treatment of malignant melanoma. However, not much is known about the effect of electrochemotherapy on the metastatic potential of tumour cells. Prevention of metastasis is an important aspect of successful treatment. It is known that metastasis can be induced by different treatment modalities. Therefore, the aim of this study was to evaluate the effect of electrochemotherapy with cisplatin on the metastatic potential of human malignant melanoma cells. The cells treated by electrochemotherapy with cisplatin, were tested for their ability to migrate and invade through Matrigel coated porous membrane. There were no significant changes observed in cell migration and invasion after electrochemotherapy. Also, there were no changes observed in cell adhesion on Matrigel. Gene expression analysis demonstrated that very low number of genes was differentially expressed after electrochemotherapy with cisplatin. Two genes, LAMB3 and CD63 involved in cell migration, were both down-regulated after electrochemotherapy with cisplatin and the expression of metastasis promoting genes was not increased after electrochemotherapy. Our data suggest that electrochemotherapy does not increase metastatic behaviour of human melanoma cells.
2009-11-01 | GSE15138 | GEO
Project description:IntroductionTavokinogene Telseplasmid Electroporation Therapy (TAVO) and Pembrolizumab therapy is being studied in subjects with immune checkpoint inhibitor (ICI) resistant melanoma. TAVO is a novel office-based local therapy shown to be effective in patients with advanced melanoma. The technique involves the direct injection of a plasmid encoding IL-12 into an accessible tumor driven by electroporation. The tumor cells have then been shown to express high levels of IL-12 resulting in a local inflammatory response within the tumor microenvironment.Presentation of caseThe patient with stage IIB, pT3b melanoma was treated with primary tumor resection and found to have a negative sentinel node biopsy. She subsequently developed regional recurrence and was treated with inguinal lymphadenectomy and adjuvant Nivolumab. Despite therapy, she had progression of disease with skin and subcutaneous metastases (in-transit lesions), brain and liver lesions, hilar and iliac nodal disease. She was transitioned to nivolumab + ipilimumab, and Talimogene Laherparepvec (T-VEC) therapy for the in-transit lesions, without success. Stereotactic radiosurgery was used for the brain metastasis. Groin subcutaneous and in-transit lesions were treated with TAVO and intravenous pembrolizumab. Serial physical exams and CT scans were used to assess response.DiscussionAll lesions treated with TAVO resolved. An abscopal response was also noted: hilar and mediastinal lymphadenopathy resolved. The liver mass and pelvic lymphadenopathy decreased in size, and her brain metastasis remained stable after radiation.ConclusionThis case suggests that combination TAVO and Pembrolizumab is a safe and effective local treatment for ICI resistant metastatic melanoma in the setting of rheumatoid arthritis. An abscopal effect was also noted through control of systemic disease.
| S-EPMC7708754 | biostudies-literature
Project description:Gynecological carcinomas affect an increasing number of women and are associated with poor prognosis. The gold standard treatment plan is mainly based on surgical resection and subsequent chemotherapy with cisplatin, 5-fluorouracil, anthracyclines, or taxanes. Unfortunately, this treatment is becoming less effective and is associated with many side effects that negatively affect patients' physical and mental well-being. Electroporation based on tumor exposure to electric pulses enables reduction in cytotoxic drugs dose while increasing their effectiveness. EP-based treatment methods have received more and more interest in recent years and are the subject of a large number of scientific studies. Some of them show promising therapeutic potential without using any cytotoxic drugs or molecules already present in the human body (e.g., calcium electroporation). This literature review aims to present the fundamental mechanisms responsible for the course of EP-based therapies and the current state of knowledge in the field of their application in the treatment of gynecological neoplasms.
| S-EPMC9026735 | biostudies-literature
Project description:Resistance to targeted therapy is an ongoing problem for the successful treatment of Stage IV metastatic melanoma. For many patients, the use of targeted therapies, such as BRAF kinase inhibitors, were initially promising yet resistance inevitably occurred. Even after combining BRAF kinase inhibitors with MEK pathway inhibitors to offset re-activation of the MAP kinase pathway, resistance is still documented. Similarly, outcomes with immune checkpoint inhibitors as monotherapy were optimistic for some patients without relapse or progression, yet the majority of patients undergoing monotherapy have progressive disease. Will immunotherapy and combination therapy trials overcome resistance in metastatic melanoma? In an effort to treat resistant disease, new clinical trials evaluating the combination of immunotherapy with other therapies, such as kinase inhibitors, adoptive cell therapy, chimeric CD40 ligand to boost costimulation, or a tumor-specific oncolytic virus enhancing granulocyte macrophage colony-stimulating factor (GM-CSF) expression, are currently underway. Updated studies on the mechanisms of resistance, immune escape and options to reinvigorate immune cells support the continued discovery of new and improved forms of therapy.
| S-EPMC5650456 | biostudies-literature
Project description:New effective therapies are greatly needed for metastatic uveal melanoma, which has a very poor prognosis with a median survival of less than 1 y. The melanocortin 1 receptor (MC1R) is expressed in 94% of uveal melanoma metastases, and a MC1R-specific ligand (MC1RL) with high affinity and selectivity for MC1R was previously developed. Methods: The 225Ac-DOTA-MC1RL conjugate was synthesized in high radiochemical yield and purity and was tested in vitro for biostability and for MC1R-specific cytotoxicity in uveal melanoma cells, and the lanthanum-DOTA-MC1RL analog was tested for binding affinity. Non-tumor-bearing BALB/c mice were tested for maximum tolerated dose and biodistribution. Severe combined immunodeficient mice bearing uveal melanoma tumors or engineered MC1R-positive and -negative tumors were studied for biodistribution and efficacy. Radiation dosimetry was calculated using mouse biodistribution data and blood clearance kinetics from Sprague-Dawley rat data. Results: High biostability, MC1R-specific cytotoxicity, and high binding affinity were observed. Limiting toxicities were not observed at even the highest administered activities. Pharmacokinetics and biodistribution studies revealed rapid blood clearance (<15 min), renal and hepatobillary excretion, MC1R-specific tumor uptake, and minimal retention in other normal tissues. Radiation dosimetry calculations determined pharmacokinetics parameters and absorbed α-emission dosages from 225Ac and its daughters. Efficacy studies demonstrated significantly prolonged survival and decreased metastasis burden after a single administration of 225Ac-DOTA-MC1RL in treated mice relative to controls. Conclusion: These results suggest significant potential for the clinical translation of 225Ac-DOTA-MC1RL as a novel therapy for metastatic uveal melanoma.
| S-EPMC6681690 | biostudies-literature
Project description:The combination of electrochemotherapy with immuno-modulatory treatments has already been explored and proven effective. However, the role of interferon alpha (IFN-?) adjuvant therapy of melanoma patients and implication on electrochemotherapy effectiveness has not been explored yet. Therefore, the aim of the study was to retrospectively evaluate the effectiveness and safety of electrochemotherapy after the previous adjuvant treatment with IFN-? in melanoma patients.The study was a retrospective single-center observational analysis of the patients with advanced melanoma, treated with electrochemotherapy after previous IFN-? adjuvant therapy. Five patients, treated between January 2008 and December 2014, were included into the study, regardless of the time point of IFN-? adjuvant therapy.Electrochemotherapy of recurrent melanoma after the IFN-? adjuvant therapy proved to be a safe and effective treatment. Patients with one or two metastases responded completely. Among patients with multiple metastases, there was a variable response rate. In one patient all 23 metastases responded completely, in second patient more than 85% of all together 80 metastases responded completely and in third patient all 5 metastases had partial response. Taking into account all metastases from all patients together there was an 85% complete response rate.The study showed that electrochemotherapy of recurrent melanoma after the IFN-? adjuvant therapy is a safe and effective treatment modality, which results in a high complete response rate, not only in single metastasis, but also in multiple metastases. The high complete response rate might be due to an IFN-? immune-editing effect, however, further studies with a larger number of patients are needed to support this presumption.
| S-EPMC4825333 | biostudies-other
Project description:Metastatic melanoma is the most aggressive and obstinate skin cancer with poor prognosis. Variant novel applicable regimens have emerged during the past decades intensively, while the most profound approaches are oncogene-targeted therapy and T-lymphocyte mediated immunotherapy. Although targeted therapies generated remarkable and rapid clinical responses in the majority of patients, acquired resistance was developed promptly within months leading to tumor relapse. By contrast, immunotherapies elicited long-term tumor regression. However, the overall response rate was limited. In view of the above, either targeted therapy or immunotherapy cannot elicit durable clinical responses in large range of patients. Interestingly, the advantages and limitations of these regimens happened to be complementary. An increasing number of preclinical studies and clinical trials proved a synergistic antitumor effect with the combination of targeted therapy and immunotherapy, implying a promising prospect for the treatment of metastatic melanoma. In order to achieve a better therapeutic effectiveness and reduce toxicity in patients, great efforts need to be made to illuminate multifaceted interplay between targeted therapy and immunotherapy.
| S-EPMC6513976 | biostudies-literature
Project description:Immune checkpoint inhibitors have changed the natural history of advanced melanoma. Despite this, a notable proportion of patients immediately relapse or develop resistance during immunotherapy, especially with the appearance of superficial metastases and consequently with a dramatic impact on clinical outcomes. Local treatment by electrochemotherapy (ECT), parallel to regional control with palliative aim, seems to release neoantigens potentially determining a significant systemic anticancer immune reactivation. The present study reported a case of a patient with metastatic melanoma receiving Pembrolizumab, electrochemotherapy and then Ipilimumab for in-transit and finally locoregional lymph nodes and distant bone metastases with experience of clinic-radiological remission. Specifically, the present patient progressed during adjuvant treatment with in-transit metastases on the scalp; he underwent two cycle of ECT obtaining partial and then unexpected and very fast nearly complete response with the Ipilimumab treatment. Concomitantly, he developed grade 4 endocrine adverse events (hypophysitis and diabetes mellitus type I) as immune-related toxicities. At 12 months from ECT the patient is in ECOG Performance Status 0 and he has resumed a regular social life. In our experience, ECT in two administrations increased and accelerated the response of Ipilimumab. The present confirmed its promising contribution in inducing a powerful immune response in order to overcome primary or acquired resistance to immune checkpoint inhibitors such as anti-programmed death antigen-1 drugs.
| S-EPMC9905651 | biostudies-literature