Compositions and methods for activating antigen presenting cells with chimeric poliovirus
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Solution Overview
Problem
Current methods for activating antigen presenting cells, such as dendritic cells, are inadequate in inducing a potent and enduring adaptive immune response, and existing poliovirus strains are cytopathogenic, leading to cell death and lysis.
Innovation Solution
Utilization of a chimeric poliovirus, like PVSRIPO, with a human rhinovirus internal ribosome entry site in the 5' untranslated region, which infects and activates antigen presenting cells without cytotoxicity, promoting a robust interferon response and sustained activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If wild-type type 1 poliovirus or Sabin 1 vaccine strain is used to infect antigen presenting cells, then cell-associated virus titers are maximized within several hours, but cell death and lysis occur within 24-36 hours
Solution Approach 1:
The patent segments the poliovirus genome by inserting a foreign nucleotide sequence (human rhinovirus 2 internal ribosome entry site) into the 5' untranslated region between the cloverleaf structure and open reading frame. This segmentation creates a chimeric virus (PVSRIPO) that separates the functions of viral replication from cytopathogenicity, allowing the virus to infect and replicate in antigen presenting cells without causing cell death and lysis.
2Reliability
If current methods are used to activate antigen presenting cells, then some activation is achieved, but a potent and enduring adaptive immune response is not induced
Solution Approach 1:
The patent converts the naturally cytopathogenic nature of poliovirus into a beneficial effect by using a chimeric version that infects antigen presenting cells and triggers robust interferon responses and sustained activation without killing the cells. The virus infection mechanism, which would normally be harmful, is transformed into a useful tool for generating potent and enduring adaptive immune responses against cancer and infections.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The chimeric poliovirus effectively activates antigen presenting cells, inducing a potent and enduring immune response, suitable for treating diseases like cancer and infections without causing cell lysis, and has demonstrated safety in clinical trials.
Implementation Method 1
Antigen presenting cells, such as macrophages and dendritic cells, express poliovirus receptor (known as PVR, or Necl-5, or CD155) and are highly susceptible to infection by type 1 strains of poliovirus
Implementation Method 2
Surprisingly, it was discovered that, unlike wild-type type 1 poliovirus and the Sabin 1 vaccine strain which are cytopathogenic to antigen presenting cells that they infect, a chimeric poliovirus, as exemplified by PVSRIPO, infects and activates antigen presenting cells (including maturation) without cytotoxicity
Data Source
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AI summary
Chimeric poliovirus is capable of activating antigen presenting cells. The activation of the antigen presenting cells may be in vitro, ex vivo, or in vivo. The activated antigen presenting cells may be administered alone or with an antigen or vaccine. The activated antigen may be loaded in vitro or ex vivo with antigen to form antigen-loaded, activated, antigen presenting cells. These may be administered therapeutically. Therapeutic administration of antigen presenting cells may be used as an adjuvant to other therapies.