Noncovalent antibody catenation on a target surface greatly increases the antigen-binding avidity.

Immunoglobulin G (IgG) antibodies are widely used for diagnosis and therapy. Given the unique dimeric structure of IgG, we hypothesized that, by genetically fusing a homodimeric protein (catenator) to the C-terminus of IgG, reversible catenation of antibody molecules could be induced on a surface where target antigen molecules are abundant, and that it could be an effective way to greatly enhance the antigen-binding avidity. A thermodynamic simulation showed that quite low homodimerization affinity of a catenator, e.g. dissociation constant of 100 µM, can enhance nanomolar antigen-binding avidity to a picomolar level, and that the fold enhancement sharply depends on the density of the antigen. In a proof-of-concept experiment where antigen molecules are immobilized on a biosensor tip, the C-terminal fusion of a pair of weakly homodimerizing proteins to three different antibodies enhanced the antigen-binding avidity by at least 110 or 304 folds from the intrinsic binding avidity. Compared with the mother antibody, Obinutuzumab(Y101L) which targets CD20, the same antibody with fused catenators exhibited significantly enhanced binding to SU-DHL5 cells. Together, the homodimerization-induced antibody catenation would be a new powerful approach to improve antibody applications, including the detection of scarce biomarkers and targeted anticancer therapies.

Treatment guidance for lung cancer patients during the COVID-19 pandemic

The global COVID-19 pandemic continues to escalate at a rapid pace inundating medical facilities and creating significant challenges globally. The risk of SARS-CoV-2 infection in cancer patients appears to be higher especially as they are more likely to present with an immunocompromised condition, either from the cancer itself or from the treatments they receive. A major consideration in the delivery of cancer care during the pandemic is to balance the risk of patient exposure and infection with the need to provide effective cancer treatment. Many aspects of the SARS-CoV-2 infection remain poorly characterized currently and even less is known about the course of infection in the context of a patient with cancer. As SARS-CoV-2 is highly contagious, the risk of infection directly affects the cancer patient being treated, other cancer patients in close proximity, and health care providers. Infection at any level for patients or providers can cause significant disruption to even the most effective treatment plans. Lung cancer patients, especially those with reduced lung function and cardiopulmonary co-morbidities are more likely to have increased risk and mortality from COVID-19 as one of its common manifestation is as an acute respiratory illness. The purpose of this manuscript is to present a practical multidisciplinary and international overview to assist in treatment for lung cancer patients during this pandemic, with the caveat that evidence is lacking in many areas. It is expected that firmer recommendations can be developed as more evidence becomes available.