Research Tool for use in Drug and Vaccine Development to
Investigate the Immune System in Response to Drug Intervention or
Disease
Princeton Docket # 12-2831
The invention is a novel computational procedure for assessing the
immune status of a subject by examining sequences from T Cells of a
subject.
More specifically presented in this technology is a method for
determining the statistical properties of the cellular machinery responsible for
creating genetic diversity in the population of immune system T-cells in a human
individual. The specific T-cell sequences in an individual change with time, but
the statistical properties of the T-cell generating machinery do not (barring
disease). These statistical properties are an intrinsic, individually unique,
characterization of immune system status, but to date, they are not accessible
to any standard analysis methodology. The purpose of this invention is to
provide an effective way of accessing those
properties.
The input to the procedure is DNA sequence data on T-cell genetic
diversity obtained by high-throughput sequencing from a blood sample. The
product is a computationally derived statistical ¿machine¿ capable of predicting
the probability that a T-cell generating stem cell will, in a generative event,
produce a T-cell with any specified genetic sequence. This provides a quantitative measure of
the ¿baseline¿ immune system diversity, against which changes due to immune
system response to challenges can be measured.
This product has numerous potential medical uses. It is a highly specific characterization of a
central property of the immune system of an individual and, as such, could be
informative about the exposure to specific antigens, the occurrence of
infection, the success of a drug treatment for infection, or about the
occurrence or progress of an auto-immune disease. Since this invention can
determine the probability that a receptor with any specific sequence will be
produced in a random T-cell generating event, it may have a role to play in
¿engineering¿ the immune system to attack disease targets, such as cancer cell
surface markers.
In summary, the invention provides access to a key property of the
immune system that has never before been accessible. The full medical utility of
this capability will only become clear after many patients and diseases have
been studied in this way.
Publications
Murugan
A., Mora T., Walczak A., Callan C.G., Statistical inference of the
generation probability of T-cell receptors from sequence repertoires
PNAS
2012 ;
published ahead of print September 17,
2012, doi:10.1073/pnas.1212755109
Mechanism and Potential Diversity of T-Cell Receptor Rearrangement
from Sequence Repertoires, Abstract for Q-Bio, Santa-Fe, NM, August 8,
2012
Keywords
Immunology, T-Cell
Receptors, VDJ rearrangement, Statistical Interference, Expectation
Maximization.
Intellectual
Property Status and technology status
Patent Pending
Princeton is seeking to identify appropriate partners for the
further development and commercialization of this technology.
Contacts
Laurie Tzodikov
Princeton
University Office of Technology Licensing ¿ (609) 258-7256¿
tzodikov@princeton.edu
Docket # 12-2831