TREATMENT OF

GLIOBLASTOMA WITH
CHIMERIC VIRUS
By: Sahil Amin

Most aggressive malignant primary

brain tumor in humans
Centered around glial cells

Glial cells provide structural and

nutritional support for neurons

Also involved in removing dead

neurons

Escapes the immune system

Cells of brain, spine are not monitored

Lack of migration to lymph nodes

Reduced MHC-I Expression

GLIOBLASTOMA

PICORNAVIRUS

Known as Poliovirus Receptor protein

Adherens junctions between epithelial cells
Found only in humans and monkeys
native to Africa and Asia

CD155

PV1(RIPO) exceedingly poor growth in tissue culture cell lines

of neuronal origin and avirulence in mice transgenic for CD155

This paper shows PV1(RIPO) can infect, propagate in cell lines

derived from malignant gliomas

Treatment with xenografts with PV1(RIPO) halted tumor

progression and resulted in tumor elimination

Paper proposes: oncolytic poliovirus recombinants with

ablated neuropathogenicity may be suitable agents in
oncologic therapy

INTERGENERIC POLIOVIRUS
RECOMBINANTS FOR THE TREATMENT OF
MALIGNANT GLIOMA

Tumor cells xenografted into anesthetized male homozygous

NCr nude mice
PV1(RIPO) propagated and purified according to established
protocols
Virus suspended in sterile PBS, injected into tail vein

METHODS

Glioma tissue was obtained during craniotomy

Tissue samples rinsed in sterile PBS
Staining performed with anti-CD155 antibody horseradish
peroxidase-conjugated anti-mouse secondary antibody

IMMUNOHISTOCHEMISTRY

90% of mice developed tumor

Mice treated with single i.v. inoculation of 2e7 pfu of PV1(RIPO)

in PBS

Marked suppression of tumor growth in all treated mice ~2

weeks

Untreated mice increased tumor size

Intratumoral replication of PV1(RIPO) results in release of

sufficient numbers of infectious particles to destroy distant
tumor foci

RESULTS

ssRNA is recognized by TLR7/8

Viral RNA can also be recognized by MDA5
Upon entry into cell, poliovirus induces MDA5 cleavage via
proteasomes and caspases
Degradation of MDA-5 correlates with poly(ADP) ribose
polymerase cleavage
PARP cleavage is a hallmark of apoptosis

DEATH OF VIRAL CELL

Intratumoral inoculation of 2e7 pfu of PV1(RIPO) resulted in

improvement of neurologic symptoms and significant increase
in survival

22 of 25 had tumor suppression, only 4 of 22 had residual

tumors

Efficient treatment of malignant gliomas by poliovirus

recombinants may depend on expression of hPVR CD155

RESULTS

Efficient oncolysis of s.c. tumor xenografts in athymic mice after i.v.

administration of PV1(RIPO) demonstrated remarkable ability of this
recombinant poliovirus to target neoplastic cells

Susceptibility of glioma cells to poliovirus depends on expression of hPVR

receptor, the Ig superfamily molecule CD155

CD155 expressed in a majority of malignant gliomas varying histopathologic

classification

CELLS STICK TO EACH OTHER VIA CD155 IN TUMORS, INCREASE CD155

ALLOWS TUMOR TO FORM

Study provides evidence that highly attenuated poliovirus/human rhinovirus

type 2 chimeras possess strong oncolytic activity against malignant gliomas

Failure of immune system allows treatment to progress

DISCUSSION

Flint S. (2009). Principles of virology (3 rd ed., Vol I). Washington, DC: ASM
Press.

Gromeier, M. (2000). Intergeneric poliovirus recombinants for the

treatment of malignant glioma. Proceedings of the National Academy of
Sciences,6803-6808.

Igney, F., & Peter, K. (2002). Immune escape of tumors: Apoptosis

resistance and tumor counterattack. Journal of Leukocyte Biology,71(6),
907-920.

Racaniello, V. Picornaviruses (2012). https://www.youtube.com/watch?

v=k3p_H_-G6Nc

Rocha, G., Deschenes, J., & Rowsey, J. (n.d.). The Immunology of Corneal
Graft Rejection.Critical Reviews in Immunology,305-325.

REFERENCES