Preclinical characterization and comparison between CD3/CD19 bispecific and novel CD3/CD19/CD20 trispecific antibodies against B-cell acute lymphoblastic leukemia: targeted immunotherapy for acute lymphoblastic leukemia / 医学前沿

The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. However, several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight, and thus its clinical use is limited. Furthermore, multiple trials have shown that approximately 30% of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells. Here, we design and characterize two novel antibodies, A-319 and A-2019. Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures, and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function. Our in vitro, ex vivo, and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells, enhancing T-cell function, mediating B-cell depletion, and eventually inhibiting tumor growth in Raji xenograft models. The two molecules are complementary in terms of efficacy and specificity profile. The activity of A-319 demonstrated superior to that of A-2019, whereas A-2019 has an additional capability to target CD20 in cells missing CD19, suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.

Parainfluenza virus pneumonia after lung transplantation :a case report and literature review / 中华器官移植杂志

Objective To explore the clinical characteristics ,diagnosis ,treatment and prognosis of parainfluenza virus (PIV) pneumonia after lung transplantation .Methods One case of PIV pneumonia after lung transplantation was retrospectively analyzed . The relevant domestic and foreign cases and literature review were summarized .Results The recipient underwent sequential bilateral lung transplantation for chronic obstructive pulmonary disease ,bullae and respiratory failure .Donor lung was sourced from donation after cardiac death .Routine anti-rejection therapy was prescribed postoperatively .At 14 months ,cough and shortness of breath lead to hospitalization for over 1 month .At 15 months ,sputum/fungal smear and culture showed that nucleic acid of PIV was positive . The definite diagnosis was PIV pneumonia after lung transplantation .After ribavirin antiviral therapy ,tracheal intubation and invasive ventilation ,followed by imipenem plus doxycycline plus anti-infective therapy ,ganciclovir antiviral therapy ,repeated bronchoscopic sputum aspiration and lavage treatment ,the patient's condition deteriorated and died from breathing failure and septic shock at 16 months .Conclusions Preventing PIV infection after lung transplantation is of vital importance .PCR is essential for a rapid detection of virus infection .However ,there is no curative treatment of PIV infection .Specific parainfluenza immunoglobulin and DAS 181 aerosol inhalation may be applied for future treatment of PIV infection in lung transplant recipients .