|
Vaccine Detail
RIPO(H3.3) |
Vaccine Information |
- Vaccine Name: RIPO(H3.3)
- Target Pathogen: Cancer
- Target Disease: Cancer
- Product Name: PVSRIPO [RIPO(H3.3)]
- Vaccine Ontology ID: VO_0007651
- Type: Recombinant vector vaccine
- Status: Research
- Host Species for Licensed Use: None
- Host Species as Laboratory Animal Model: Mouse
- Antigen: RIPO(H3.3) expresses and processes the foreign H3.3(K27M) antigen, which is a high affinity HLA-A2-restricted tumor neoantigen (Mosaheb et al., 2020).
- Vector:
- Immunization Route: Intramuscular injection (i.m.)
- Description: mRIPO(H3.3) enhances survival in a mouse glioma model (Mosaheb et al., 2020). RIPO(H3.3) also induces type I IFN activation of human DCs (Mosaheb et al., 2020).
|
Host Response |
Mouse Response
- Vaccination Protocol: Heterozygous hCD155- and AAD(HLA-A2)-tg C57Bl6 mice were obtained by cross breeding hCD155-tg mice with AAD-tg mice. Murine CT2AAAD_H3.3K27M malignant gliomas were implanted intracerebrally in hCD155/AAD-tg mice (Mosaheb et al., 2020). AAD_hCD155 transgenic mice were immunized by i.m. inoculation (day 1), implanted with CT2A_AADH3.3K27M cells for orthotopic tumor initiation (day 7), boosted with the same regimen (day 14), and followed for assessment of weight and neurological status. Mice were euthanized after losing 15% of their max. weight.
- Immune Response: mRIPO(H3.3)-immunized mice survived significantly longer than their mRIPOδ6-immunized littermates. CD8 depletion abrogates the anti-tumor effect of mRIPO(H3.3) immunization (Mosaheb et al., 2020). I.m. immunization with mRIPO(H3.3) significantly extended the survival of CT2A_AADH3.3K27M tumor-bearing mice when compared to mRIPOδ6 immunized mice. In a repeat experiment, mRIPOδ6/mRIPO(H3.3)-immunized animals received intraperitoneal inoculations of anti-CD8 antibodies for CD8 T cell depletion (initiated 7 days prior to tumor implantation). This abolished the therapeutic effect of mRIPO(H3.3) immunization. Thus, PVSRIPO vector-induced H3.3K27M-specific CD8 T cell responses successfully target intracerebral H3.3K27M+ malignant gliomas in vivo (Mosaheb et al., 2020).
|
References |
Mosaheb et al., 2020: Mosaheb MM, Dobrikova EY, Brown MC, Yang Y, Cable J, Okada H, Nair SK, Bigner DD, Ashley DM, Gromeier M. Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity. Nature communications. 2020; 11(1); 524. [PubMed: 31988324].
|
|