Mathematical Modeling Insights into Improving CAR T cell Therapy for Solid Tumors: Antigen Heterogeneity and Bystander Effects [PDF]
As an adoptive cellular therapy, Chimeric Antigen Receptor T-cell (CAR T-cell) therapy has shown remarkable success in hematological malignancies, but only limited efficacy against solid tumors. Compared with blood cancers, solid tumors present a unique set of challenges that ultimately neutralize the function of CAR T-cells.
arxiv +1 more source
The role of antigen-competitive dynamics in regulating the immune response [PDF]
The clonal expansion of T cells during an infection is tightly regulated to ensure an appropriate immune response against invading pathogens. Although experiments have mapped the trajectory from expansion to contraction, the interplay between mechanisms that control this response are not fully understood.
arxiv +1 more source
Regulation of T cell expansion by antigen presentation dynamics [PDF]
An essential feature of the adaptive immune system is the proliferation of antigen-specific lymphocytes during an immune reaction to form a large pool of effector cells. This proliferation must be regulated to ensure an effective response to infection while avoiding immunopathology.
arxiv +1 more source
Molecular tug of war reveals adaptive potential of an immune cell repertoire [PDF]
The adaptive immune system constantly remodels its lymphocyte repertoire for better protection against future pathogens. Its ability to improve antigen recognition on the fly relies on somatic mutation and selective expansion of B lymphocytes expressing high-affinity antigen receptors.
arxiv
Influence of telopeptides on the structural and physical properties of polymeric and monomeric acid-soluble type I collagen [PDF]
Currently two factors hinder the use of collagen as building block of regenerative devices: the potential antigenicity, and limited mechanical strength in aqueous environment. Polymeric collagen is naturally found in the cross-linked state and is mechanically tougher than the monomeric, cross-link-free (acid-soluble) collagen ex vivo.
arxiv +1 more source
The effects of symmetry on the dynamics of antigenic variation [PDF]
In the studies of dynamics of pathogens and their interactions with a host immune system, an important role is played by the structure of antigenic variants associated with a pathogen. Using the example of a model of antigenic variation in malaria, we show how many of the observed dynamical regimes can be explained in terms of the symmetry of ...
arxiv +1 more source
Identifying the genetic basis of antigenic change in influenza A(H1N1) [PDF]
Determining phenotype from genetic data is a fundamental challenge. Influenza A viruses undergo rapid antigenic drift and identification of emerging antigenic variants is critical to the vaccine selection process. Using former seasonal influenza A(H1N1) viruses, hemagglutinin sequence and corresponding antigenic data were analyzed in combination with 3-
arxiv +1 more source
Prediction, dynamics, and visualization of antigenic phenotypes of seasonal influenza viruses [PDF]
Human seasonal influenza viruses evolve rapidly, enabling the virus population to evade immunity and re-infect previously infected individuals. Antigenic properties are largely determined by the surface glycoprotein hemagglutinin (HA) and amino acid substitutions at exposed epitope sites in HA mediate loss of recognition by antibodies.
arxiv +1 more source
Computational model for tumor response to adoptive cell transfer therapy [PDF]
One of the barriers to the development of effective adoptive cell transfer therapies (ACT), specifically for genetically engineered T-cell receptors (TCRs), and chimeric antigen receptor (CAR) T-cells, is target antigen heterogeneity. It is thought that intratumor heterogeneity is one of the leading determinants of therapeutic resistance and treatment ...
arxiv
Sequence-Based Nanobody-Antigen Binding Prediction [PDF]
Nanobodies (Nb) are monomeric heavy-chain fragments derived from heavy-chain only antibodies naturally found in Camelids and Sharks. Their considerably small size (~3-4 nm; 13 kDa) and favorable biophysical properties make them attractive targets for recombinant production.
arxiv