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Journal For Immunotherapy of Cancer May 2022Immune checkpoint inhibitors (ICIs) have been increasingly used in patients with various cancers and have shown efficient therapeutic outcomes. However, fewer than 40%...
BACKGROUND
Immune checkpoint inhibitors (ICIs) have been increasingly used in patients with various cancers and have shown efficient therapeutic outcomes. However, fewer than 40% of cases across multiple cancer types show a response to ICIs. Therefore, developing more efficient combinational approaches with ICIs and revealing the underlying mechanisms are important goals for achieving rapid clinical transformation and application.
METHODS
The effects on antitumor immunity activity of albendazole (ABZ) and the synergistic effects of ABZ with CD73 blockade were investigated in the melanoma B16F10 and the Lewis lung cancer tumor-bearing immune-competent mice models. The mechanism of ABZ reducing PD-L1 protein level through suppressing UBQLN4 was identified and validated through immunoprecipitation-mass spectrometry and molecular methods. Bioinformatics and anti-PD-1 therapy melanoma patients samples analysis were used to assess the level of UBQLN4/PD-L1 in the therapeutic efficacy of anti-PD-1 therapy.
RESULTS
ABZ induces CD8 T cell activity and subsequent immunotherapy response associated with suppression of PD-L1 protein level. Mechanistically, we revealed that ABZ promotes ubiquitin-mediated degradation of PD-L1 via suppressing UBQLN4, which was bound to PD-L1 and stabilized PD-L1 protein. Preclinically, genetic deletion or target inhibition of CD73 showed synergistic effects with ABZ treatment in the immune-competent mice models. Significantly, UBQLN4 and PD-L1 levels were higher in the tumor region of responders versus non-responders and correlated with better progression-free survival and overall survival in anti-PD-1 therapy melanoma patients.
CONCLUSIONS
Our findings revealed a previously unappreciated role of ABZ in antitumor immunity by inducing ubiquitin-mediated PD-L1 protein degradation, identified predictors for assessing the therapeutic efficacy of anti-PD-1 therapy, and provided novel therapeutic possibility by combination treatment of ABZ and CD73 blockade in cancers.
Topics: Albendazole; Animals; B7-H1 Antigen; Humans; Immunotherapy; Melanoma; Mice; Ubiquitin
PubMed: 35577504
DOI: 10.1136/jitc-2021-003819 -
Indian Pediatrics Sep 1993
Review
Topics: Albendazole; Cysticercosis; Echinococcosis; Humans; Nervous System Diseases
PubMed: 8125597
DOI: No ID Found -
Nanomedicine (London, England) Oct 2017Initially emerging as a widely used clinical antiparasitic drug, albendazole (ABZ) has been increasingly recognized as an effective anticancer agent due to its... (Review)
Review
Initially emerging as a widely used clinical antiparasitic drug, albendazole (ABZ) has been increasingly recognized as an effective anticancer agent due to its outstanding advantage, in other words, low toxicity to normal cells but high effectiveness against parasites and some tumors. The major challenge is its poor water solubility and subsequently low bioavailability. This article thus first reviews the brief achievements in using ABZ to treat parasites and cancers, and summarizes the basic mechanisms of action of ABZ. Then this article critically reviews recent nanotechnological strategies, in other words, formulating/conjugating it with carriers into nanoformulations, in practices of improving aqueous solubility and efficacy in treatment of tumors and parasites. Our expert opinions in this field are provided for more effective delivery of ABZ to treat tumors and parasites in vivo.
Topics: Albendazole; Animals; Antineoplastic Agents; Antiparasitic Agents; Biological Availability; Chemistry, Pharmaceutical; Drug Carriers; Drug Liberation; Humans; Nanoparticles; Solubility
PubMed: 28954575
DOI: 10.2217/nnm-2017-0102 -
Acta Parasitologica Sep 2023Data regarding albendazole monotherapy for cystic echinococcosis (CE) are scarce, especially in children. We report our experience treating CE in children with...
BACKGROUND
Data regarding albendazole monotherapy for cystic echinococcosis (CE) are scarce, especially in children. We report our experience treating CE in children with albendazole monotherapy.
METHODS
A retrospective case series, 2005-2021, assessing factors leading to albendazole monotherapy, demographic, clinical, duration of treatment and follow-up, and outcome (changes in cyst size and side effects) characteristics.
RESULTS
Overall, we identified 18 patients with 31 cysts; liver: 68% (n = 21), lungs: 29% (n = 9), and kidney: 3% (n = 1). Mean cyst size was 4.5 ± 2.6 cm. Reasons for administrating albendazole monotherapy were small (< 4 cm) cyst size (56%), difficulty to operate (33%) and comorbidity (22%). Duration of treatment (range 1-32 months) was 1, 2-3, 4-6 and > 6 months in 28% (n = 5), 39% (n = 7), 17% (n = 3) and 17% (n = 3) of children, respectively. Duration of follow up (range 1-87 months) was 1, 2-3, 4-6 and > 6 months in 11% (n = 2), 11% (n = 2), 17% (n = 3) and 61% (n = 11) of children, respectively. Overall, 83% (n = 15) of patients experienced lack of cyst growth, and 72% (n = 13) experienced reduction in cyst size, while 44% (n = 8) experienced reduction larger than 50%. Full resolution was noted in 22% (n = 4) of patients. In three cases (17%) treatment failure was recorded: one (6%) recurrence, and two cases (11%) of cyst growth. Neutropenia was recorded in two patients (11%), and liver enzymes elevation was recorded in six patients (33%).
CONCLUSIONS
Albendazole monotherapy may be an adequate treatment for selected cases of CE disease in children, especially in CE with small, hepatic cysts.
Topics: Humans; Child; Albendazole; Retrospective Studies; Echinococcosis; Cysts; Echinococcosis, Hepatic
PubMed: 37466820
DOI: 10.1007/s11686-023-00699-6 -
Dermatologic Clinics Apr 2003In 1961 Brown and his team discovered that thiobendazoles were highly effective against gastrointestinal nematodes. This discovery led to the development of albendazole,... (Review)
Review
In 1961 Brown and his team discovered that thiobendazoles were highly effective against gastrointestinal nematodes. This discovery led to the development of albendazole, the most recent of the benzimidazolic drugs. Albendazole is used against numerous animal and human parasites and it is the authors' first choice as drug treatment of cutaneous larva migrans.
Topics: Albendazole; Antiparasitic Agents; Humans
PubMed: 12757251
DOI: 10.1016/s0733-8635(02)00085-2 -
Cutis May 2022
Topics: Albendazole; Alopecia; Humans
PubMed: 35856765
DOI: 10.12788/cutis.0548 -
Indian Pediatrics Jan 2015
Topics: Albendazole; Anticestodal Agents; Child; Echinococcosis; Female; Hepatitis, Autoimmune; Humans; Transaminases
PubMed: 25638200
DOI: No ID Found -
Acta Tropica May 2003The pharmacokinetics and toxicity of albendazole, mebendazole and praziquantel are extensively reviewed, drawing on original published work and reviews in the open... (Review)
Review
The pharmacokinetics and toxicity of albendazole, mebendazole and praziquantel are extensively reviewed, drawing on original published work and reviews in the open scientific literature and on assessments by international agencies and official regulatory bodies in Europe and the USA. Information about human and veterinary medical uses and adverse reactions is evaluated. The totality of the non-clinical information available about these long-established drugs may not comply with current official guidelines for new medicines but reasons are given why the "deficiencies" are only apparent and the data gaps can be replaced by other results, largely obtained from the target species and the many years of clinical experience of safe use of these drugs in humans and animals.
Topics: Albendazole; Animals; Anthelmintics; Humans; Mebendazole; Praziquantel; Toxicity Tests
PubMed: 12745134
DOI: 10.1016/s0001-706x(03)00031-7 -
Indian Journal of Pediatrics 1993
Topics: Albendazole; Brain Diseases; Child; Cysticercosis; Humans
PubMed: 8244473
DOI: 10.1007/BF02860518 -
The American Journal of Tropical... Oct 2018
Topics: Albendazole; Anthelmintics; Drug Administration Schedule; Echinococcosis; Humans; Practice Guidelines as Topic; Treatment Outcome
PubMed: 30141399
DOI: 10.4269/ajtmh.18-0609