Vaccination with EGF was safe and provoked an increase in anti-EGF antibody titers and a decrease in serum EGF. There was a direct correlation between antibody response and survival. There was a direct correlation between decrease in serum EGF and survival. In patients younger than 60 years, vaccination was associated with increased survival.

The epidermal growth factor receptor (EGFR) proto-oncogene is frequently overexpressed in tumors of epithelial origin. This event is thought to be causative for tumor development and progression and henceforth associated with poor prognosis. The recent considerable interest in developing EGFR-targeting agents resulted in derivation of the monoclonal, humanized, neutralizing antibody h-R3, which binds to the extracellular domain of EGFR with high affinity and strongly inhibits EGFR-dependent cellular transformation. Thus, treatment of A431 squamous cell carcinoma cells with h-R3 in either 2-dimensional or 3-dimensional culture resulted in appreciable antimitotic effects through induction of the G1 arrest. Although h-R3 does not appear to have a direct proapoptotic activity in this setting, it inhibits production of the vascular endothelial growth factor (VEGF) by A431 cells both in vitro and in vivo. In the latter case, h-R3 treatment (0.25-1 mg/mouse; every other day per 2 weeks) not only significantly reduced VEGF mRNA expression of A431 tumors growing subcutaneously in SCID mice but also resulted in reduction of the overall microvascular density (MVD), disappearance of dilated "mother vessels," as well as in suppression of tumor growth followed by regression of established tumors. This apparent antiangiogenic activity of h-R3 was associated with reduction in Ki67-positive tumor cell fraction and (unlike in vitro) also with an elevated apoptotic index, the latter indicative of a cytotoxic mode of action in vivo. Taken together, h-R3 is a promising new antagonist of the EGFR oncogene, the anticancer properties of which are associated with combined and potent antiproliferative, antiangiogenic and proapoptotic activity.

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.

Nimotuzumab plus chemoradiotherapy was safe and provided statistically significant objective response. A Phase III in patients with similar characteristics will be launched.

KEY WORDSepidermal growth factor, epidermal growth factor receptor, EGF vaccine, non-small Treatment of NSCLC Patients with an EGF-Based Cancer VaccineReport of a Phase I Trial ABSTRACT Epidermal Growth Factor (EGF) promotes tumor cell proliferation and survival upon binding to its receptor. We have developed a new active specific immunotherapy based on EGF deprivation. In the present paper, we show the results of a Phase I trial in 43 patients with advanced non-small cell lung cancer (NSCLC) who received the EGF vaccine. Patients who had already received first line therapy were randomized to receive a single or double dose of the EGF vaccine, weekly for four weeks and monthly thereafter. No significant toxicity was seen after vaccination. Adverse events consisted primarily of fever, chills, nausea, vomiting and flushing. Fifteen patients (39%) developed a good antibody response (GAR) against EGF. The geometric mean of the antibody titer was higher in the double dose group. EGF concentration was quantified in serum. An inverse correlation between anti-EGF antibody titers and EGF concentration was seen after immunization. Vaccinated patients achieved median survival times of 8.23 months from randomization. Patients who received the double dose of treatment showed a trend toward increased survival in comparison with patients who received the single dose. GAR and patients in whom the serum EGF decreased below the 168 pg/ml cut-off point had a significantly better survival when compared to poor responders or patients in which the EGF levels were not considerably reduced. Our results confirm the immunogenicity of the EGF vaccine in the treatment of patients with advanced stage NSCLC. Antibody titers and serum EGF levels appear to correlate with patient survival.

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 nimotuzumab, an anti-EGFR antibody, in COVID-19 patients. Patients received from one to three infusions together with other drugs included in the national guideline. Results: 41 patients (31 severe and 10 moderate) received nimotuzumab. The median age was 62 years and the main comorbidities were hypertension, diabetes and cardiovascular disease. The antibody was very safe and the 14-day recovery rate was 82.9%. Inflammatory markers decreased over time. Patients did not show signs of fibrosis. Conclusion: Nimotuzumab is a safe antibody that might reduce inflammation and prevent fibrosis in severe and moderate COVID-19 patients. Clinical Trial Registration: RPCEC00000369 ( rpcec.sld.cu ).

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BackgroundThe progressive decline in the immune function during ageing is termed immunosenescence. Previous studies have reported differences between males and females in the distribution and cell responses of lymphocyte subsets. Most studies of immunosenescence have been done in populations of industrialized countries living in a rather cold environment, and facing lower antigenic challenges such as Cytomegalovirus (CMV). The aim of this study was to determine the effect of ageing on lymphocytes in a population with a high prevalence of CMV infection in all ages, and to compare gender differences related to the immunosenescence markers.ResultsDifferent populations of peripheral blood leukocytes from healthy young and old IgG-CMV seropositive individuals were examined using flow cytometry. With age, the number and frequency of B cells and T cells significantly decreased, while highly differentiated T cells increased. Such changes were different in males and females. The age-associated decline of less differentiated lymphocyte subsets (CD19, CD4 and CD8 cells) and the increase of highly differentiated T cells were more prominent in females. In males, there were no significant changes in CD19, CD4 and CD8 subsets but there was a significant increase in the proportion of highly differentiated T cells.ConclusionShifts in lymphocyte subsets distribution were influenced by age and gender in an IgG-CMV seropositive population. These results suggest different patterns of immunosenescence in respect to gender differences. These patterns could have implications in the design of immunotherapy in the elderly.