Background: Over-expression of epidermal growth factor receptor in esophageal cancer is associated with poor prognosis. The present study was conducted to evaluate safety and preliminary efficacy of nimotuzumab, a humanized anti-EGFR antibody in combination with radiation and chemotherapy in advanced esophageal tumours. Patients and Methods: A Phase II clinical trial was conducted, where patients received cisplatin, 5-fluorouracil, and radiotherapy, either alone or combined with six weekly infusions of nimotuzumab at the dose of 200 mg. Safety was the primary endpoint. The antitumoral objective response rate was the secondary endpoint. Epidermal growth factor receptor expression, KRAS mutation status and anti-idiotypic response were also evaluated. Results: Sixty-three patients were included in the study. Thirty patients were entered into the control group, and thirty-three patients received the treatment with nimotuzumab. The antibody was very well tolerated. Objective response rate was 47.8 % (nimotuzumab group) and 15.4 % (control group). Disease control rate was 60.9 % (nimotuzumab group) and 26.9 % (control group). Response and disease control rate were higher in patients with EGFR overexpressing tumors. Conclusion: Nimotuzumab plus chemoradiotherapy was safe and provided statistically significant objective response. A Phase III in patients with similar characteristics will be launched.

Background: Lung injury and STAT1 deficit induce EGFR overexpression in SARS-CoV-2 infection. Patients & methods: A phase I/II trial was done to evaluate the safety and preliminary effect of nimotu... Plain language summary Background: After SARS-CoV-2 infection, many cells in the lung express a new receptor called EGFR. Overexpression of EGFR can worsen the pulmonary disease and provoke fibrosi...

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a recent outbreak of coronavirus disease (COVID-19). In Cuba, the first case of COVID-19 was reported on March 11, 2020. Elderly individuals with multiple comorbidities are particularly susceptible to adverse clinical outcomes in the course of SARS-CoV-2 infection. During the outbreak, a local transmission event took place in a nursing home in Villa Clara province, Cuba, in which 19 elderly residents tested positive for SARS-CoV-2. Methods: Based on the increased susceptibility to cytokine release syndrome, inducing respiratory and systemic complications in this population, 19 patients were included in an expanded access clinical trial to receive itolizumab, an anti-CD6 monoclonal antibody. Results: All patients had underlying medical conditions. The product was well tolerated. After the first dose, the course of the disease was favorable, and 18 of the 19 patients (94.7%) were discharged clinically recovered with negative real-time reverse transcription polymerase chain reaction test results at 13 days. After one dose of itolizumab, circulating IL-6 decreased within the first 24–48 h in patients with high baseline values, whereas in patients with low levels, this concentration remained over low values. To preliminarily assess the effect of itolizumab, a control group was selected among the Cuban COVID-19 patients that did not receive immunomodulatory therapy. The control subjects were well matched regarding age, comorbidities, and severity of the disease. The percentage of itolizumab-treated, moderately ill patients who needed to be admitted to the intensive care unit was only one-third of that of the control group not treated with itolizumab. Additionally, treatment with itolizumab reduced the risk of death 10 times as compared with the control group. Conclusion: This study corroborates that the timely use of itolizumab in combination with other antivirals reduces COVID-19 disease worsening and mortality. The humanized antibody itolizumab emerges as a therapeutic alternative for patients with COVID-19. Our results suggest the possible use of itolizumab in patients with cytokine release syndrome from other pathologies.

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 cel... Lay abstract In COVID-19 patients, inflammation is associated with the progression of the disease. This inflammation comes from immune system activation in response to SARS-COV-2. Itolizumab is an ...

Monoclonal antibody (mAb) ior c5 is an IgG1, which recognizes a glycoprotein tumor specific antigen IOR C2 over expressed in the surface of colon and ovarian cancer cells. The aim of the present work was to evaluate the diagnostic efficacy of the 99mTc-labeled mAb ior c5 for the detection of colorectal tumors, its metastases and recurrences. Methods: Eighty six patients with colorectal or anal cancer, mean age 57 +/- 13 yrs, were involved in a phase I/II multicentric, open clinical trial to assess the ability of Radioimmunoscintigraphy (RIS) with 99mTc- mAb ior c5 to detect those tumors. 74 patients received 1 mg of c5 labeled with 1480-1850 MBq to determinate diagnosis efficacy and safety of murine mAb by intravenously (i.v) bolus injection (group 1). In order to evaluate pharmacokinetic, bio distribution and dosimetry of this radiolabel molecule, 12 patients received 3 mg of labeled ior c5. Planar anterior and posterior images of the lesion sites and suspected metastases were acquired at 2, 4 and 18-24 hours after injection using a matrix size 128 x128 and 500 Kcounts per view. SPECT were scanned at 5 hr post-injection, using a 360° circular orbit with 64 images. HAMA response was measured in serum at 2, 4, 8 and 12 week post-administration. Results: Labeling efficiency was (97.8 ± 0.6) %. No adverse reactions or side effects were observed. Overall sensitivity, specificity, accuracy, positive and negative predictive values of the immunoscintigraphy were 95.80%, 100%, 96.51%, 100.0% and 82.35%, respectively. Unknown metastases were detected in 37 of 86 cases (43.02%). No HAMA response was found. Conclusions: Immunoscintigraphy with 99mTc -labeled mAb ior c5 could be a useful procedure for the diagnosis and follow-up of the patients with colorectal tumors, its metastasis and recurrences.

Introduction: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a recent outbreak of Coronavirus Disease (COVID-19). In Cuba, the first case of COVID-19 was reported on March 11. Elderly with multiple comorbidities are particularly susceptible to adverse clinical outcomes in the course of SARS CoV-2 infection. During the outbreak, a local transmission event took place in a nursing home in Villa Clara province, Cuba, in which nineteen elderly residents were positive for SARS-CoV-2. Methods: Based on the increased susceptibility to viral-induced cytokine release syndrome inducing respiratory and systemic complications in this population, the patients were included in an expanded access clinical trial to receive itolizumab, an anti-CD6 monoclonal antibody. Results: All the patients had underlying medical conditions. The product was well tolerated. After the first dose, the course of the disease was favorable and 18 out of 19 (94.7%) patients were discharged clinically recovered with negative RT-PCR at 13 days (median). One dose of itolizumab, circulating IL-6 decreased in the first 24-48 hours in patients with high baseline values, whereas in patients with low levels, this concentration remained over low values. To preliminary assess the effect of itolizumab, a control group was selected among the Cuban COVID-19 patients, which did not receive immunomodulatory therapy. Control subjects were well-matched regarding age, comorbidities and severity of the disease. Every three moderately ill patients treated with itolizumab, one admission in intensive care unit (ICU) was prevented. Discussion/Conclusion: Itolizumab was well tolerated. Its effect is associated with a reduction and controlling IL-6 serum levels. Moreover, treated patients had a favorable clinical outcome, considering their poor prognosis. This treatment is associated significantly with a decrease the risk to be admitted in ICU and reduced 10 times the risk of death. This study corroborates that the timely use of itolizumab, in combination with other antiviral and anticoagulant therapies, is associated with a reduction the COVID-19 disease worsening and mortality. The humanized antibody itolizumab emerges as a therapeutic alternative for patients with COVID-19 and suggests its possible use in patients with cytokine release syndrome from other pathologies.