PVS-RIPO

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PVS-RIPO , also PVSRIPO , is a genetically modified poliovirus that is being studied as an active ingredient against certain types of cancer . It belongs to the cancer cell-killing (oncolytic) viruses and has been used in isolated studies to treat a malignant brain tumor ( glioblastoma ).

properties

PVS-RIPO is an attenuated and hardly pathogenic oncolytic virus. It is derived from the orally effective polio vaccine (serotype 1 or Sabin strain of the poliovirus). In the virus genome , the internal ribosomal entry point ( IRES ) was replaced by one from human rhinovirus type 2 (HRV-2) using recombinant DNA technology , which means that there is no longer any replication in neurons .

The acronym PVS-RIPO comes from the English name p olio v irus ( S abin) r hinovirus I RES p oliovirus o pen reading frame .

Mechanism of action

PVS-RIPO selectively replicates in tumor cells that express the CD155 ("poliovirus receptor ") . CD155 is a transmembrane protein of the immunoglobulin superfamily and a tumor antigen . CD155 plays a role in tumor cell migration , invasion and metastasis . Due to the heterologous HRV2-IRES, PVS-RIPO is only replicated in susceptible, non- neuronal cells. In contrast to chemotherapy, normal cells are hardly attacked. It is assumed that effectiveness comes about less through cell lysis than through triggering an antineoplastic immune response .

Potential areas of application

In experiments with rhesus monkeys that had been infected with various types of cancer, the virus was able to destroy the cancer, whereby the test animals did not suffer any consequential damage. PVS-RIPO was approved for human studies by the US FDA in 2012.

PVS-RIPO received media attention in 2015 after a report in the US news magazine 60 Minutes , in which early results in the experimental treatment of glioblastoma were reported. PVS-RIPO was administered directly into the tumor via a catheter through the patient's skull. In May 2016, Duke University in the US state of North Carolina , where the therapy is being developed, announced that the FDA had granted the drug Breakthrough Therapy status .

Since CD155 is not only expressed to an increased extent in brain tumor cells, but also in a number of other types of tumor cells, for example breast cancer, lung cancer, colorectal cancer and liver cancer, these cells can also be infected with PVS-RIPO. The effect is investigated in xenograft animal models.

Web links

  • Michael C. Brown, Matthias Gromeier: Oncolytic Immunotherapy Through Tumor-specific Translation and Cytotoxicity of Poliovirus . In: Discovery Medicine, No. 19 (2015), pp. 359-365. PMID 26105699 . PMC 4780852 (free full text).

Individual evidence

  1. ↑ a b NCI Drug Dictionary - recombinant oncolytic poliovirus PVS-RIPO
  2. ↑ J. Ylä-Pelto, L. Tripathi, P. Susi: Therapeutic Use of Native and Recombinant Enteroviruses. In: Viruses. Volume 8, number 3, February 2016, p. 57, doi : 10.3390 / v8030057 , PMID 26907330 , PMC 4810247 (free full text).
  3. ↑ a b PVS-RIPO heals cancer according to rponline of April 2, 2015, accessed on December 11, 2016
  4. ↑ Oncolytic therapeutic approaches according to deutschlandfunk.de from June 14, 2015, accessed on December 11, 2016
  5. ^ Poliovirus wins breakthrough status , Duke Today, May 16, 2016.
  6. ↑ C. Goetz et al .: Oncolytic poliovirus against malignant glioma . Future Virology, Vol. 6, No. 9 (2011), pp. 1045-1058. doi : 10.2217 / fvl.11.76 , PMC 3187927 (free full text)
  7. ↑ Eda K. Holl et al .: Recombinant oncolytic poliovirus, PVSRIPO, has potent cytotoxic and innate inflammatory effects, mediating therapy in human breast and prostate cancer xenograft models . Oncotarget, No. 7 (2016); Pp. 79828-79841. doi : 10.18632 / oncotarget.12975 , PMC 5346754 (free full text)