Interesting Antibody Papers

Here we highlight two antibody papers, one from the past one more recent. The more recent one talks about developing an affinity maturation model. The older one is a refresher on the Developability Index — how to computationally harness hydrophobicity and accessible surface areas to predict aggregation.

Mouse antibody maturation model — the most expanded (common) clones might not be the ones with highest affinities here (van Kampen lab). The authors of the paper define a model of affinity maturation. The main take-home message of the paper is that the ‘most expanded’ clones might not be the ones with highest affinity — expanded clones are assumed to be the ones ‘responding’ to the antigenic challenge. The model is based on Ordinary Differential Equations, tracing cell fate in a germinal center. The model was compared to experimental expansion data from lymph nodes for accuracy. In each such model one needs to assume a lot of parameters, such as which day post-immunization do we start somatic hypermuatation? The paper is a very nice example of a model of maturation and a good starting point for tracing references citing germinal center biology and numbers for parameters used for models (also the general canon of construction of such models!).

Developability index here. (Trout lab at MIT). The authors touch on a very important subject of antibody developability: after you produced your ab binder, does it have physicochemical characteristics which are suitable to carry on with it as a therapeutic. Such characteristics include stability, expression yields and aggregation propensity. Aggregation propensity is one of the most important factors here as it affects the pharmacokinetics of the drug as well as shelf life. In this manuscript, authors address attempt to predict the aggregation propensity of antibodies. As background data, they use twelve antibodies whose long term stability has been measured over several years. To develop a computational method to predict antibody aggregation propensity, they use a score which combines hydrophobicity and electrostatic factors. The hydrophobicity is an adapted SAP score which the authors developed previously, and whose main parameters are the exposed residue area and hydrophobicity of the residue as defined by Black and Mould. The electrostatics are calculated using PROPKA. Since combining the scores into a predictive model involved parametrization, they use seven of the antibodies to adjust the coefficients. They use the rest to demonstrate that their model has predictive power. Calculation of their models requires a structure of an antibody which they obtain using WAM. Take home messages? It is a nice dataset to play with aggregation prediction and it demonstrates how to calculate electrostatics and hydrophobicity of a molecule.