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Efroni, S.

Publications and source records attributed to Efroni, S..

2 recordsLinked to original sources

Digital therapeutics for distributed response to global pandemics

Despite advances in the development of drugs and vaccines, the spread of infectious diseases remains an imminent threat to our global health, in extreme cases potentially having detrimental consequences. At present our response to this threat is based on physically distributing therapeutic material, which utilizes the same transportation networks that support the spread of the infectious agent itself. Such competition is at risk of failure in the face of a rapidly spreading pathogen, especially given the inevitable delay from the initial outbreak to the development and execution of our response. Moreover, based on our existing transportation networks, we show that such physical distribution is intrinsically inefficient, leading to an uneven concentration of the therapeutic within a small fraction of destinations, while leaving the majority of the population deprived. This suggests that outrunning a virulent epidemic can only be achieved if we develop a mitigation strategy that bypasses the existing distribution networks of biological and chemical material. Here we propose such a response, utilizing digitizable therapeutics, which can be distributed as digital sequence files and synthesized on location, exposing an extremely efficient mitigation scheme that systematically outperforms physical distribution. Our proposed strategy, based for example on nucleic acid therapeutics, is plausibly the only viable mitigation plan, based on current technology, that can face a violently spreading pathogen. Complementing the current paradigm, which ranks drugs based on efficacy, our analysis demonstrates the importance of balancing efficacy with distributability, finding that in some cases the latter plays the dominant role in the overall mitigation efficiency.

bioinformatics

Mice developing mammary tumors evolve T cell sequences shared with human breast cancer patients

Cancer immunotherapy by checkpoint blockade proves that an effective immune response to a tumor can be induced clinically. However, little is known about the evolution of tumor-associated T-cell receptor (TCR) repertoires without intervention. Here we studied TCR repertoire evolution in mice spontaneously developing mammary tumors; we sequenced peripheral blood alpha and beta TCRs of CD4+CD62L+CD44- T cells monthly for 8 months in 10 FVB/NJ mice transgenic at the Erbb2 locus, all developing tumors; 5 FVB/NJ mice without the transgene were age-matched controls. Sequences were either private (restricted to one mouse) or public (shared among mice); public sequences were either exclusive to the tumor group or inclusive among different groups. We now report that 1), public AA sequences were each encoded by many different nucleotide sequences (NT) recombinations (convergent recombination; CR); 2) mice developing tumors evolved tumor-exclusive public sequences, derived initially from private or from inclusive public sequences; and 3) tumor-exclusive public sequences in mice were also present among published public TCR sequences from human breast cancer patients. These cross-species tumor-exclusive TCR sequences manifested high CR; but the AA sequences shared by mice and humans did not share NT sequences. Thus, tumor-exclusive TCR AA sequences across species are selected from different NT recombination events. The roles of tumor-exclusive TCR repertoires in advancing or inhibiting tumor development and the effects of tumor immunotherapy on these T cells remain to be seen.

cancer biology