RESUMO
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 controls matching with the nimotuzumab patients, were selected using a "propensity score" method. The 14-day recovery rate of the nimotuzumab cohort was 72 vs. 42% in the control group. Controls had a higher mortality risk (RR 2.08, 95% CI: 1.79, 2.38) than the nimotuzumab treated patients. The attributable fraction was 0.52 (95% CI: 0.44%; 0.58), and indicates the proportion of deaths that were prevented with nimotuzumab. Our preliminary results suggest that nimotuzumab is a safe antibody that can reduce the mortality of severe and critical COVID-19 patients.
Assuntos
Tratamento Farmacológico da COVID-19 , Estudos de Coortes , Humanos , Estudos Retrospectivos , SARS-CoV-2RESUMO
Metastatic castration-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. Activation of the human epidermal growth factor receptor 1 (HER1) in prostate cancer contributes to metastatic progression as well as to disease relapse. Here, we determined the toxicity and immunogenicity of a HER1-based cancer vaccine in CRPC patients included in a phase I clinical trial. CRPC patients (n = 24) were intramuscularly vaccinated with HER1 vaccine consisting of the extracellular domain of HER1 molecule (ECD) and very small size proteoliposome from Neisseria meningitidis (VSSP) and Montanide ISA-51 VG as adjuvants. Patients were included in five groups according to the vaccine dose (100, 200, 400, 600, and 800 µg). The primary endpoints were safety and immunogenicity. The anti-HER1 antibodies were measured by an ELISA, the recognition of an HER1 positive tumor cell line and the inhibition of HER1 phosphorylation by sera were determined by flow cytometry and western blot analysis, respectively. The HER1-specific T cell response was assessed by determination of IFN-γ-producing T cells using ELISpot assay. The vaccine was well tolerated. No grade III or IV adverse events were reported. High titers of anti-HER1 antibodies were observed in most of the evaluated patients. There were no significant differences regarding the geometric means of the anti-HER1 titers among the dose groups except the group of 100 µg in which antibody titers were significantly lower. A Th1-type IgG subclasses pattern was predominant in most patients. Only patients receiving the higher doses of vaccine showed significant tumor cell recognition and HER1 phosphorylation inhibition by hyperimmune sera. Forty two percent of the patients showed a specific T cell response against HER1 peptides pool in post-treatment samples. There was a trend toward survival benefit in those patients showing high anti-HER1 specific antibody titers and a significant association between cellular immune response and clinical outcome.
RESUMO
A phase I clinical trial was conducted in patients with stage III/IV breast cancer who were treated with the anti-idiotype mAb 1E10 specific to an Ab1 mAb able to react specifically with N-glycolyl-containing gangliosides and with antigens expressed on human melanoma and breast carcinoma cells. Patients were treated with 1 or 2 mg of aluminum hydroxide-precipitated 1E10 mAb every other week for six injections. Two patients at each dose were reimmunized 7-9 months after completing the induction phase. In hyperimmune sera from eight of the nine patients who received at least four doses of anti-Id vaccine preparations, strong specific responses were observed both against 1E10 mAb and NeuGc-GM3 ganglioside (Ab3 Id+Ag+). Nonclassical Ab1' antibodies (Id-Ag+) were also elicited by 1E10 mAb vaccine treatment. There were no differences between the two levels of dose tested in relation to toxicity and immunogenicity. No evidence of serious or unexpected effects was observed.