Papers by Mayra Ramos Suzarte
Clinical & Translational Immunology, 2020
Objectives. COVID-19 can lead to a hyperinflammatory state. CD6 is a glycoprotein expressed on ma... more Objectives. COVID-19 can lead to a hyperinflammatory state. CD6 is a glycoprotein expressed on mature T lymphocytes which is a crucial regulator of the T-cell activation. Itolizumab is a humanised antibody targeting CD6. Nonclinical and clinical data in autoimmune diseases indicate that it lowers multiple cytokines primarily involving the Th1/Th17 pathway. The primary objective of this study was to assess the impact of itolizumab in arresting the lung function deterioration of COVID-19 patients. Secondary objectives included safety, duration of ventilation, 14-day mortality and evaluation of interleukin 6 concentration. Methods. Patients with confirmed SARS-CoV-2 received itolizumab in combination with other therapies included in the national protocol for COVID-19. Results. Seventy critical, severe or moderate patients were treated with itolizumab in 10 Cuban hospitals. Median age was 68, and 94% had comorbidities. After 72 h, most patients improved the PO 2 /FiO 2 ratio and reduced FiO2 requirements. Ventilation time was 8 days for critical and 1 day for severe cases. Ten patients had related adverse events while 3 subjects developed related serious events. In 30 patients, interleukin 6 decreased in individuals with high level and did not change in those with lower concentration. Fourteen-day lethality rate was 4% and 18% for moderate and severe patients, respectively. The proportion of moderate or severe patients with ventilation or death at day 14 was 9.8%. Time to treatment,
European Journal of Cancer Supplements, 2007
Hybridoma, Apr 1, 2001
Ior egf/r3, a neutralizing monoclonal antibody (mAb) against Epidermal Growth Factor Receptor (EG... more Ior egf/r3, a neutralizing monoclonal antibody (mAb) against Epidermal Growth Factor Receptor (EGFR) was generated at the Cuban Institute of Oncology. Immunoscintigraphic studies in 148 patients with this 99-m Technetium (99 Tc) labeled mAb, showed a high sensitivity and specificity for in vivo detection of epithelial tumors. To study safety, pharmacokinetic and immunogenicity of ior egf/r3 at high doses, a phase I clinical trial was conducted. Nineteen patients with advanced epithelial tumors received 4 mAb intravenous infusions at 6 dose levels: from 50 to 500 mg. Previously, immunoscintigraphic images using the same mAb labeled with 99 Tc were acquired. Blood samples were collected for pharmacokinetic analysis and HAMA response. After mAb therapy, objective response was classified according to WHO criteria. Ior egf/r3 was well tolerated in spite of the high-administered doses. Only a severe adverse reaction consisting of hypotension and lethargy was observed. In 13 patients, selective accumulation of 99 Tc-labeled mAb was observed at the site of the primary tumor or the metastasis. Pharmacokinetic analysis revealed that elimination half-life and the area under the time-concentration curve increased linearly with dose. HAMA response was detected in 17 patients. After 6 months of mAb therapy, 4 patients had stable disease. One patient had a tumor partial remission after 3 cycles of ior egf/r3.
Proceedings for Annual Meeting of The Japanese Pharmacological Society, 2018
Pharmaceutics, 2020
Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease characterized by an ove... more Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease characterized by an overexpression of epidermal growth factor receptor (EGFR). Nimotuzumab is a recombinant humanized monoclonal antibody against human EGFR. The aim of this study was to develop a population pharmacokinetic model for nimotuzumab and to identify demographic and clinical predictive factors of the pharmacokinetic variability. The population pharmacokinetics (PopPK) of nimotuzumab was characterized using a nonlinear mixed-effect modeling approach with NONMEM®. A total of 422 log-transformed concentration-versus-time datapoints from 20 patients enrolled in a single-center phase I clinical trial were used. Quasi steady state approximation of the full TMDD (target-mediated drug disposition) model with constant target concentration best described the concentration-time profiles. A turnover mediator was included which stimulates the non-specific clearance of mAb in the central compartment in order to e...
(24%), and surgery only (10.5%). The 5-year overall survival (OS) was 60.5% and 10-year survival ... more (24%), and surgery only (10.5%). The 5-year overall survival (OS) was 60.5% and 10-year survival rate was 56%. The 5-year relapse free survival was 57.3%. Ten-year OS was indistinguishable between the group that was treated with the combination of surgery/CT and the group that had received CT only (60% versus 61.5%, respectively). In multivariate analysis, high grade lymphoma and complete response were the only significant prognostic factors for OS. Conclusion: The clinical presentation of small intestinal lymphoma is non specific. The prognosis is good. With advancement in endoscopy and interventional radiology, surgery has a limited role in diagnosis. It seems that there is no benefit in terms of overall survival to operating on patients with PSIL.
Background: Since the COVID-19 outbreak an unprecedented challenge for healthcare systems around ... more Background: Since the COVID-19 outbreak an unprecedented challenge for healthcare systems around the world has been placed. In Cuba, the first case of COVID-19 was reported on March 11. Elderly with multiple comorbidities have been the most risky population. Although most patients present a mild to moderate disease, some have developed severe symptoms. One of the possible mechanisms underlying rapid disease progression is a cytokine storm, in which interleukin (IL) -6 seems to be a major mediator. Itolizumab is a humanized recombinant anti-CD6 monoclonal antibody (MAb), with the ability of reducing serum interferon gamma (INF-γ), tumour necrosis factor alpha (TNFα) and IL-6. Based on these previous results in patients with psoriasis and rheumatoid arthritis, an expanded access clinical trial was approved by the Cuban regulatory agency for COVID-19 critically, severely and moderately ill patients. Results: We show here a short kinetic of IL-6 serum concentration in the first 24 COVI...
Bionatura, 2020
Nimotuzumab, humanized monoclonal antibody, directed against the epidermal growth factor receptor... more Nimotuzumab, humanized monoclonal antibody, directed against the epidermal growth factor receptor: highly expressed protein in malignant tumors of epithelial origin. It has been registered for head and neck tumors since 2002. To determine the effectiveness of Nimotuzumab in head and neck cancer through the combined meta-analysis technique. A search was conducted in PubMed, in an indexed magazine with the words “Nimotuzumab”, “head and neck,” 48 articles published by Cuban and foreign authors were detected between April 1, 2005, and July 31, 2019, in which the results of clinical studies conducted with the monoclonal antibody Nimotuzumab are described. Seven clinical trials conducted in Cuba from 2005-2019 with Nimotuzumab are described; three Phase I / II (with 14, 10 and 10 patients respectively), a Phase II / III with 106 patients, a Phase II with 37 patients, two Phase IV (with 386 and 225 patients each) and a study promoted by the Researcher with 17 patients. From these studies,...
Seminars in Oncology, 2018
One of the most known oncogenes is the epidermal growth factor receptor (EGFR) family. It activat... more One of the most known oncogenes is the epidermal growth factor receptor (EGFR) family. It activates multiple signaling cascades which promote carcinogenesis and immune evasion. Therefore, these molecules have been extensively targeted in cancer immunotherapy. Beyond EGFR signaling cascade inhibition, some of these agents are able to induce T cell activation transforming a passive therapy into a vaccine-like effect. Nimotuzumab is an IgG1 humanized MAb directed against the extracellular domain of the EGFR blocking the binding to its ligands. It possesses unique pharmacodynamics properties, which allow treating patients for long-term period and with very low toxicity. Based on its clinical effect, nimotuzumab has been approved in Cuba and abroad for the treatment of different epithelial tumors. Recently, new potential mechanisms of action of nimotuzumab involving the activation of the innate and adaptive immune response have been reported. This review summarizes the main properties of nimotuzumab in comparison with others EGFR specific monoclonal antibodies highlighting its capacity to activate an effective immune response. In addition, differential clinical effect of this antibody and ongoing clinical trials to deeply characterize the biomarkers of clinical benefit are shown.
Frontiers in Public Health
EGFR signaling is an important regulator of SARS-CoV induced lung damage, inflammation and fibros... more EGFR signaling is an important regulator of SARS-CoV induced lung damage, inflammation and fibrosis. Nimotuzumab is a humanized anti-EGFR antibody registered for several cancer indications. An expanded access study was conducted to evaluate the safety and recovery rate of severe and critical patients with confirmed SARS-CoV-2 infection, treated with nimotuzumab in combination with the standard of care in the real-world scenario. The antibody was administered as an intravenous infusions every 72 h, up to 5 doses. In order to assess the impact of nimotuzumab, the recovery rate was compared with a paired retrospective cohort. Control patients received standard treatment according the national protocol but not nimotuzumab. Overall, 1,151 severe or critical patients received nimotuzumab in 21 hospitals of Cuba. Median age was 65 and 773 patients had at least one comorbidity. Nimotuzumab was very well-tolerated and mild or moderate adverse events were detected in 19 patients. 1,009 contro...
Archives of Clinical and Medical Case Reports
A hypercytokinemia ending in pulmonary and systemic illness occurs in severe COVID-19 patients. M... more A hypercytokinemia ending in pulmonary and systemic illness occurs in severe COVID-19 patients. Mature T lymphocytes express CD6, a molecule that regulates antigen specific responses of T cells. Itolizumab is an anti-CD6 antibody, which inhibits the proliferation of naïve T-cells and reduces the secrInflammationetion of pro-inflammatory cytokines.
Bionatura, 2020
La calidad de vida y la supervivencia son variables a tener en cuenta en ensayos clínicos de paci... more La calidad de vida y la supervivencia son variables a tener en cuenta en ensayos clínicos de pacientes oncológicos. Es importante investigar la relación que existe entre ellas para los distintos tipos de cáncer. Se unieron las bases de datos de todos los pacientes oncológicos incluidos en los ensayos clínicos que se ejecutaron en el país, en el período 2000-2020. La calidad de vida se evaluó a través de las encuestas utilizadas en cada protocolo de investigación. Se realizó un análisis del tiempo transcurrido entre la inclusión del paciente y el fallecimiento para determinar el tiempo de supervivencia. Se comprobó que las variables de supervivencia de los pacientes incluidos en ensayos clínicos, mostraron valores superiores a los reportados para los pacientes con similares localizaciones del tumor no incluidos en estas investigaciones. Las localizaciones de mayor supervivencia fueron: pulmón (14.03 meses), cabeza y cuello (19.63 meses) y esófago (16.85 meses). En el caso de la calid...
Results in Immunology, 2012
T cells are involved in the pathogenesis of rheumatoid arthritis (RA). CD6 is a co-stimulatory mo... more T cells are involved in the pathogenesis of rheumatoid arthritis (RA). CD6 is a co-stimulatory molecule, predominantly expressed on lymphocytes, that has been linked to autoreactive responses. The purpose of this study was to evaluate the safety, immunogenicity and preliminary efficacy of itolizumab, a humanized anti-CD6 monoclonal antibody, in patients with active rheumatoid arthritis. Fifteen patients were enrolled in a phase I, open-label, dose-finding study. Five cohorts of patients received a weekly antibody monotherapy with a dose-range from 0.1 to 0.8 mg/kg. Itolizumab showed a good safety profile, with no severe or serious adverse events reported so far. No signs or symptoms associated with immunosuppression were observed in the study. Objective clinical responses were achieved in more than 80% of patients after treatment completion, and these responses tend to be sustained afterwards. This clinical study constitutes the first evidence of the safety and positive clinical effect of a monotherapy using an anti-CD6 antibody in patients with rheumatoid arthritis.
Cancer Biology & Therapy, 2007
Cancer Biology & Therapy, 2008
This manuscript has been published online, prior to printing.Once the issue is complete and page ... more This manuscript has been published online, prior to printing.Once the issue is complete and page numbers have been assigned, the citation will change accordingly. Radioimmunotherapy (RIT) may improve the management of malignant gliomas. A Phase I clinical trial was performed to evaluate, for the first time, the toxicity and clinical effect of an intracavitary administration of a single dose of Nimotuzumab (h-R3) labeled wit 188 Re. Nimotuzumab is a humanized monoclonal antibody directed against epidermal growth factor receptors. Three patients with anaplastic astrocytoma (AA) and 8 with glioblastoma multiforme (GBM) were intended to be treated with 3 mg of mAb labelled with 10 or 15 mCi of 188 Re. In patients treated with 10 mCi (n = 6) transitory worsening of pre-existing neurological symptoms were observed. Two patients treated with 15 mCi (n = 4) developed early severe neurological symptoms and one also developed late severe toxicity (radionecrosis). In the group treated with 10 mCi, 1 GBM patient died in progression 6 months after the treatment, 2 patients (1 GBM and 1 AA) developed stable disease during 3 months. One GBM patient had partial response for more than 1 year and 2 patients (1 GBM and 1 AA) were asymptomatic and in complete response after 3 years of treatment. Maximal tolerated dose of the radioimmunoconjugate 188 Re-Nimotuzumab was 3 mg of the h-R3 labelled with 10 mCi of 188 Re. The radioimmunoconjugate showed a high retention in the surgical created resection cavity and the brain adjacent tissues with a mean value of 85.5% of the injected dose one hour post-administration. This radioimmunoconjugate may be relatively safe and a promising therapeutic approach for treating high grade gliomas.
Cancer Biology & Therapy, 2006
The poor prognosis of patients with high-grade glioma has led to the search for new therapeutic s... more The poor prognosis of patients with high-grade glioma has led to the search for new therapeutic strategies. More than half of these tumors overexpress Epidermal Growth factor Receptor (EGFR). h-R3 is a humanized monoclonal antibody that recognize the EGFR external domain with high affinity, inhibiting tyrosine kinase activation. In order to evaluate safety, immunogenicity and preliminary efficacy of h-R3 in newly diagnosed high-grade glioma patients, we conducted a Phase I/II trial. Patients received six weekly infusions of h-R3 at the dose of 200 mg in combination with external beam radiotherapy. Twenty-nine patients (mean age, 45 years and median KPS 80) were entered into the study. Tumor types were: glioblastoma (GB) (16 patients), anaplastic astrocytoma (AA) (12 patients) and anaplastic oligodendroglioma (AO) (1 patient). All patients underwent debulking surgery or biopsy before entering the trial. The antibody was very well tolerated. No evidences of grade 3/4 adverse events were detected. None of the patients developed acneiform rash or allergic reactions. One patient developed a positive anti-idiotypic response. Objective response-rate was 37.9% (17.2% complete response, 20.7% partial response) while stable disease occurred in 41.4% of the patients. With a median follow up time of 29 months, the median survival is 22.17 months for all subjects. Median survival time (MST) is 17.47 months for GB, whereas MST is not reached for AA patients.
Immunotherapy, 2021
In COVID-19, the inflammatory cytokine-release syndrome is associated with the progression of the... more In COVID-19, the inflammatory cytokine-release syndrome is associated with the progression of the disease. Itolizumab is a monoclonal antibody that recognizes human CD6 expressed in activated T cells. The antibody has shown to be safe and efficacious in the treatment of moderate to severe psoriasis. Its effect is associated with the reduction of pro-inflammatory cytokines release, including IFN-γ, IL-6 and TNF-α. Here, we report the outcome of three severe and critically ill COVID-19 patients treated with itolizumab as part of an expanded access protocol. Itolizumab was able to reduce IL-6 concentrations in all the patients. Two of the three patients showed respiratory and radiological improvement and were fully recovered. We hypothesize this anti-inflammatory therapy in addition to antiviral and anticoagulant therapy could reduce COVID-19 associated morbidity and mortality.
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Papers by Mayra Ramos Suzarte