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Clinical Immunology (Orlando, Fla.) Sep 2022(Leukaemia derived) dendritic cells (DC, DC) are potent stimulators of anti-leukaemic activity in acute myeloid leukaemia (AML) and can be generated with...
Immunomodulatory kits generating leukaemia derived dendritic cells do not induce blast proliferation ex vivo: IPO-38 as a novel marker to quantify proliferating blasts in acute myeloid leukaemia.
(Leukaemia derived) dendritic cells (DC, DC) are potent stimulators of anti-leukaemic activity in acute myeloid leukaemia (AML) and can be generated with immunomodulatory kits containing granulocyte-macrophage-colony-stimulating-factor (GM-CSF), prostaglandin-E (PGE), prostaglandin-E (PGE) and/or picibanil (OK-321). Potential adverse effects initiated through kits, especially the proliferation of blasts, must be ruled out to ensure treatment safety. We quantified proliferating blasts with the proliferation markers CD71 and Ki-67 and the novel proliferation marker IPO-38 before and after kit treatment ex vivo. IPO-38 hereby appeared to be the most sensitive marker; a combination with CD71 may add value when assessing proliferation kinetics. Kit treatment did not or only slightly (<5%) induce blast proliferation in most cases. An induction of blast proliferation was only found in single cases and could be compensated by DC-induced anti-leukaemic activity in most times. Overall, we appraise kit treatment to be safe in vivo.
Topics: Biomarkers; Cell Proliferation; Dendritic Cells; Humans; Leukemia, Myeloid, Acute; Prostaglandins; Prostaglandins E
PubMed: 35908638
DOI: 10.1016/j.clim.2022.109083 -
Drug Research Sep 2022Antitumor activities of L-MTP-PE (Liposome entrapped myuramyl tripeptide phosphatidylethanolamine) in the combination treatment with chemo- or immune-therapeutic...
Effects of Liposome-Entrapped Muramyl Tripeptide Phosphatidylethanolamine (L-MTP-PE) on the Tumor Growth and Survival of Mice Bearing Syngeneic Tumor in Combination with a Chemotherapeutic or Immunomodulatory Agent.
Antitumor activities of L-MTP-PE (Liposome entrapped myuramyl tripeptide phosphatidylethanolamine) in the combination treatment with chemo- or immune-therapeutic antitumor agents against various syngeneic tumors were tested.Against Meth A fibrosarcoma solid tumor system, L-MTP-PE showed slight but statistically significant elongation of survival days against 5-FU monotherapy in spite of its non-effect on tumor growth, when combined with 5-FU. Against liver metastasis model of M5076 carcinoma, L-MTP-PE showed a tendency of elongation of survival days by its single drug treatment, however, elongation with statistical significance was observed in the combination treatment with 5-FU in comparison with control group.These data suggest that L-MTP-PE seems to elongate the survival days of the solid tumor bearing mice and the liver metastasis model basically due to its saving effect on chemotherapeutic drug-induced immunosuppression. In the combination with an immunotherapeutic agent in mice, TNF production induced by another biological response modifier OK-432 was potentiated when primed with L-MTP-PE. L-MTP-PE also potentiate the antitumor effect of OK-432 possibly through the enhanced production of TNF-α. Combination of L-MTP-PE and OK-432 is considered to be a candidate for a new treatment model for cancer.
Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Drug Carriers; Fluorouracil; Immunologic Factors; Immunomodulating Agents; Liposomes; Liver Neoplasms; Mice; Phosphatidylethanolamines; Picibanil
PubMed: 35767993
DOI: 10.1055/a-1847-7312 -
Cancer Cell International Jun 2022Colorectal cancer (CRC) with pulmonary metastasis usually indicates a poor prognosis, whereas patients may benefit from adoptive cell therapy. Tumor-specific cytotoxic T...
BACKGROUND
Colorectal cancer (CRC) with pulmonary metastasis usually indicates a poor prognosis, whereas patients may benefit from adoptive cell therapy. Tumor-specific cytotoxic T lymphocytes (CTLs) have been reported as a promising treatment for CRC. However, the antitumor effect of CTLs remains limited partially due to insufficient production of effector cells via the activation by antigen-presenting dendritic cells (DCs).
METHOD
This study showed that a combination of CD40 mAb and Picibanil (OK-432) could significantly enhance the activation of CTLs by DCs, both in vitro and in vivo. Flow cytometry, colon cancer mouse model, and pathological staining were employed to demonstrate the specific functions.
RESULTS
This approach promoted the maturation of DCs, augmented the production of stimulatory cytokines, and suppressed the secretion of inhibitory cytokines. Additionally, it facilitated the killing efficiency of CTLs via stimulating their proliferation while restraining the number of Tregs, concomitantly with the positive regulation of corresponding cytokines. Furthermore, the combined unit could hurdle the expansion of tumor cells on metastatic lungs in the colon cancer mouse model.
CONCLUSION
Collectively, the combination of CD40-mAb and OK-432 facilitated the maturation of DCs and enhanced the cytotoxicity of T cells, promising therapeutic approach against CRC.
PubMed: 35715855
DOI: 10.1186/s12935-022-02630-x -
Transfusion Medicine and Hemotherapy :... Feb 2022Myeloid leukaemic blasts can be converted into leukaemia-derived dendritic cells (DC), characterised by the simultaneous expression of dendritic- and...
Interferon Gamma Secretion of Adaptive and Innate Immune Cells as a Parameter to Describe Leukaemia-Derived Dendritic-Cell-Mediated Immune Responses in Acute Myeloid Leukaemia in vitro.
INTRODUCTION
Myeloid leukaemic blasts can be converted into leukaemia-derived dendritic cells (DC), characterised by the simultaneous expression of dendritic- and leukaemia-associated antigens, which have the competence to prime and enhance (leukaemia-specific) immune responses with the whole leukaemic antigen repertoire. To display and further specify dendritic cell (DC)- and DC-mediated immune responses, we analysed the interferon gamma (IFNy) secretion of innate and adaptive immune cells.
METHODS
DC/DC were generated from leukaemic whole blood (WB) with (blast)modulatory Kit-I (granulocyte-macrophage colony-stimulating factor [GM-CSF] + Picibanil [OK-432]) and Kit-M (GM-CSF + prostaglandin E1) and were used to stimulate T cell-enriched immunoreactive cells. Initiated anti-leukaemic cytotoxicity was investigated with a cytotoxicity fluorolysis assay. Initiated IFNy secretion of T, NK, CIK, and iNKT cells was investigated with a cytokine secretion assay (CSA). IFNy positivity was additionally evaluated with an intracellular cytokine assay (ICA). Recent activation of leukaemia-specific cells was verified through addition of leukaemia-associated antigens (LAA; WT-1 and Prame).
RESULTS
We found Kit-I and Kit-M competent to generate mature DC and DC from leukaemic WB without induction of blast proliferation. Stimulation of immunoreactive cells with DC/DC regularly resulted in an increased anti-leukaemic cytotoxicity and increased IFNy secretion of T, NK, and CIK cells, pointing to the significant role of DC/DC in leukaemia-specific alongside anti-leukaemic reactions. Interestingly, an addition of LAA did not further increase IFNy secretion, suggesting an efficient activation of leukaemia-specific cells. Here, both the CSA and ICA yielded comparable frequencies of IFNy-positive cells. Remarkably, the anti-leukaemic cytotoxicity positively correlated with the IFNy secretion in T, T, T, and NK cells.
CONCLUSION
Ultimately, the IFNy secretion of innate and adaptive immune cells appeared to be a suitable parameter to assess and monitor the efficacy of in vitro and potentially in vivo acute myeloid leukaemia immunotherapy. The CSA in this regard proved to be a convenient and reproducible technique to detect and phenotypically characterise IFNy-secreting cells. In respect to our studies on DC-based immunomodulation, we were able to display the potential of DC/DC to induce or improve leukaemia-specific and anti-leukaemic activity.
PubMed: 35221867
DOI: 10.1159/000516886 -
Otolaryngologia Polska = the Polish... Jun 2021<b>Introduction:</b> Recurrent thyroglossal duct cyst after surgery is not a rare condition and first-line treatment has not been established...
<b>Introduction:</b> Recurrent thyroglossal duct cyst after surgery is not a rare condition and first-line treatment has not been established yet.<br/><br/> <b>Aim:</b> Evaluation of outcomes and complications of OK-432 treatment in patients with recurrent thyroglossal duct cyst after surgery. <br/><br/> <b>Material and methods:</b> This study is designed as a case series with planned data collection at Tohoku Medical and Pharmaceutical University and Fukase Clinic. Five patients with recurrent thyroglossal duct cyst after surgery received this therapy between January 2014 and February 2020 on an outpatient basis, without hospitalization. OK-432 solution was injected into the lesion using an 18- or 27-gauge needle, depending on the location and size of the lesion, as well as on possible complications.<br/> <br/> <b>Results:</b> Lesions showed marked reduction or total shrinkage in all patients, with no local scarring or deformity at the injection site. Side effects manifested as local pain at the site of injection and fever (37.5-38.5°C) observed in three patients, but the symptoms resolved within a few days.<br/> <br/> <b>Conclusions:</b> Since OK-432 therapy is simple, easy, safe and effective, it can be used as an alternative to surgery in the treatment of recurrent thyroglossal duct cyst after surgery.
Topics: Child; Humans; Picibanil; Thyroglossal Cyst
PubMed: 35175217
DOI: 10.5604/01.3001.0014.9073 -
Journal of Pediatric Surgery May 2022Sclerotherapy is frequently employed in treating lymphatic malformations (LMs), and multiple agents, practitioners and strategies exist. This review investigates the...
PURPOSE
Sclerotherapy is frequently employed in treating lymphatic malformations (LMs), and multiple agents, practitioners and strategies exist. This review investigates the reported efficacy and safety of sclerosants in the pediatric population.
METHODS
Adhering to PRISMA guidelines, multiple databases were queried without linguistic or temporal restriction. Inclusion criteria were patients aged 0-18 exclusively receiving injection sclerotherapy for the treatment of LMs with follow-up data. Data abstracted included agent, dose, anatomic site and key outcome measures including complications (major/minor) and resolution rates (>95% reduction in volume). Critical appraisal was undertaken using the MINORS tool.
RESULTS
Forty-eight studies met the inclusion criteria with a mean MINORS score of 0.65 ± 0.08. Included studies yielded 886 patients, across nearly 30 years. The overall observed rate of success was 89%, with variable follow-up across publications (6 weeks - 10 years). Most reported LMs were macrocystic (82%) and had a higher resolution rate than mixed/microcytic variants (89%, 71%, 34%, p<0.01) For head/neck LMs, rates of complete regression for OK-432, bleomycin, and doxycycline were 67% ± 27% (n = 26), 91% ± 53% (n = 34) and 85% ± 16% (n = 52) respectively. Major complications were most commonly reported with OK-432, including airway compromise or subsequent operation.
CONCLUSIONS
In pediatric patients treated for LM by sclerotherapy, complication rates were low. Macrocystic lesions respond well but success rates were modest at best for microcystic disease. Differences in agent utilization were noted between high and low resourced contexts; despite its lack of federal approval, OK-432 was the most reported agent. Further prospective research is warranted. LOE: 3a.
Topics: Child; Humans; Infant; Lymphatic Abnormalities; Neck; Picibanil; Retrospective Studies; Sclerosing Solutions; Sclerotherapy; Treatment Outcome
PubMed: 35151497
DOI: 10.1016/j.jpedsurg.2021.12.056 -
Gynecology and Minimally Invasive... 2021This is a case report of a uterine cancer with the International Federation of Gynecology and Obstetrics staging 3c2 with the initial clinical presentation of...
This is a case report of a uterine cancer with the International Federation of Gynecology and Obstetrics staging 3c2 with the initial clinical presentation of postmenopausal vaginal bleeding in August 2015. Endometrium biopsy showed invasive nests of poorly differentiated grade 3 endometrioid adenocarcinoma. The patient received robotic surgery including total hysterectomy, bilateral salpingo-oophorectomy, bilateral pelvic lymph node dissection, para-aortic lymph node dissection, and washing cytology. The final pathology showed an endometrioid carcinoma with myometrium invasion up to 85% and para-aortic and pelvic lymph nodes invasion. The patient received six courses of adjuvant chemotherapy (paclitaxel and carboplatin) with concurrent chemoradiotherapy after the surgery. Later, immunotherapy with Picibanil (OK-432) and interleukin-2 (IL-2) was given, and cancer did not recur for 34 months until tumor recurrence at the liver dome and bilateral lung was noted by positron-emission tomography scan in July 2018. The patient received laparoscopic surgery for intra-abdominal tumor excision in December 2018, and the tumor found extended to the right diaphragm, liver surface, omentum, bilateral flank to pelvic peritoneum, Douglas pouch, and upper rectum. We continued the immunotherapy with OK-432, IL-2, Aldara cream (imiquimod), and later on, virotherapy (human papillomavirus vaccine). The immune risk profiles showed T-cells' proliferation and alteration of the Th1/Th2 activation after immunotherapy and virotherapy. Proctectomy with colon-anal anastomosis and cytoreduction surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) (doxorubicin and paclitaxel) was performed in January 2019. After the surgery, the patient received chemotherapy (topotecan, paclitaxel, lipodox, and carboplatin) and continued the immunotherapy. The immune risk profiles showed CD4, CD4/CD8 increase after HIPEC and immunotherapy. The patient continued the therapy until May 2020.
PubMed: 34485069
DOI: 10.4103/GMIT.GMIT_153_20 -
European Radiology Dec 2021To review the effectiveness and safety of chemical ablation using ethanol or OK-432 for the treatment of TGDCs (thyroglossal duct cysts). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To review the effectiveness and safety of chemical ablation using ethanol or OK-432 for the treatment of TGDCs (thyroglossal duct cysts).
METHODS
MEDLINE and EMBASE databases were searched up to May 29, 2020, to identify studies reporting the safety and efficacy of chemical ablation using ethanol or OK-432 for the treatment of TGDCs. The search query consisted of synonyms of thyroglossal duct cysts and ethanol or OK-432 ablation. The pooled success and complication rates were calculated using the inverse variance method to calculate weights, and pooled proportions were determined using the DerSimonian-Laird random-effects method.
RESULTS
Seven original articles including a total of 129 patients were included. The efficacy of chemical ablation was acceptable, with a pooled success rate of 70% (95% CI, 47-86%). The pooled success rate of ethanol ablation was superior to that of OK-432 ablation, although with equivocal statistical significance (84% vs. 51%, p = 0.055). Repeat ethanol ablation achieved a pooled success rate of 47% (95% CI, 24-71%). The chemical ablation procedures were safe, with a pooled major complication rate of 0.9% (95% CI, 0.1-5.8%).
CONCLUSIONS
Chemical ablation using ethanol or OK-432 for the treatment of TGDCs had acceptable success and low complication rates, and repeat treatment after initial failure was also feasible. In addition, it is an inexpensive and simple procedure and could therefore be considered a first-line treatment for TGDCs.
KEY POINTS
• The efficacy of chemical ablation using ethanol or OK-432 was acceptable, with a pooled success rate of 70% (95% CI, 47-86%). The pooled success rate of ethanol ablation was superior to that of OK-432 ablation, although with equivocal statistical significance (84% vs. 51%, p = 0.055). • Repeat ethanol ablation was also feasible, with a pooled success rate of 47% (95% CI, 24-71%). • The chemical ablation procedures were safe, with a pooled major complication rate of 0.9% (95% CI, 0.1-5.8%).
Topics: Ablation Techniques; Ethanol; Humans; Picibanil; Sclerotherapy; Thyroglossal Cyst
PubMed: 34003346
DOI: 10.1007/s00330-021-08033-2 -
Acta Oto-laryngologica May 2021Ranula is a rare benign cystic lesion in the floor of the mouth, which can herniate through the mylohyoid muscle and become a plunging ranula. Treatment for ranulas is... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Ranula is a rare benign cystic lesion in the floor of the mouth, which can herniate through the mylohyoid muscle and become a plunging ranula. Treatment for ranulas is currently surgical excision of the sublingual gland. Sclerotherapy with OK-432 is a well-established treatment of lymphatic malformations, but not yet thoroughly evaluated on ranulas. Objectives: To evaluate sclerotherapy of ranulas with OK-432 in a randomized double-blinded trial.
MATERIALS AND METHODS
20 patients with plunging or intraoral ranula were randomized to two double-blinded injections with OK-432 or saline. Effect on the ranula and evaluation of symptoms and QOL were investigated.
RESULTS
Treatment response differed significantly between OK-432 and placebo, = .041(student's T-test). All patients with intraoral ranulas had a complete response, but only 1/4 of the patients with plunging ranula. The inflammatory reaction after injection with OK-432 caused a mild to moderate impact on QOL. No serious complications were observed.
CONCLUSION
This study suggests that sclerotherapy with OK-432 in ranula is a very effective treatment for intraoral ranulas, but possibly less useful in plunging ranulas.
SIGNIFICANCE
This is a limited study, but we believe that sclerotherapy with OK-432 should be recommended as primary treatment at least for intraoral ranulas.
Topics: Adolescent; Adult; Antineoplastic Agents; Child; Double-Blind Method; Female; Humans; Injections, Intralesional; Male; Middle Aged; Picibanil; Prospective Studies; Ranula; Sclerotherapy; Young Adult
PubMed: 33775200
DOI: 10.1080/00016489.2021.1889660 -
Otolaryngology--head and Neck Surgery :... Dec 2021The role of sclerotherapy for vascular lesions of the head and neck is well established. However, the efficacy of sclerotherapy for benign cystic lesions of the head and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The role of sclerotherapy for vascular lesions of the head and neck is well established. However, the efficacy of sclerotherapy for benign cystic lesions of the head and neck is less clear. The objective of this review is to determine the efficacy and safety of sclerotherapy for benign cystic lesions of the head and neck.
DATA SOURCES
PubMed/MEDLINE, Cochrane Library, and Embase.
REVIEW METHODS
The PRISMA guidelines (Preferred Reporting Systems for Systematic Reviews and Meta-analyses) were followed for this systematic review. Studies of patients with benign head and neck cystic masses treated primarily with sclerotherapy were included. Thirty-two studies met criteria for inclusion.
RESULTS
A total of 474 cases of sclerotherapy were reviewed. Agents comprised OK-432, ethanol, doxycycline, tetracycline, and bleomycin. Lesions in the analysis were ranula, thyroglossal duct cyst, branchial cleft cyst, benign lymphoepithelial cyst, parotid cyst, thoracic duct cyst, and unspecified lateral neck cyst. A total of 287 patients (60.5%) had a complete response; 132 (27.9%) had a partial response; and 55 (11.6%) had no response. OK-432 was the most widely utilized agent, with a higher rate of complete response than that of ethanol (62.0% vs 39.4%, = .015). Fifty-three cases (11.2%) required further surgical management. One case of laryngeal edema was reported and managed nonoperatively.
CONCLUSION
Sclerotherapy appears to be a safe and efficacious option for benign cystic lesions if malignancy is reliably excluded. Efficacy rates are comparable to those of sclerotherapy for vascular malformations. The rate of serious complications is low, with 1 incident of airway edema reported in the literature.
Topics: Branchioma; Cysts; Ethanol; Humans; Lymphocele; Neck; Parotid Diseases; Picibanil; Ranula; Sclerotherapy; Thyroglossal Cyst; Vascular Malformations
PubMed: 33755513
DOI: 10.1177/01945998211000448