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Updated: Aug 8, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Systemic oncolytic herpes virus therapy of poorly immunogenic prostate cancer metastatic to lung
Susan Varghese1, Samuel D Rabkin, Petur G Nielsen
1Molecular Neurosurgery Laboratory, Department of Neurosurgery, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
Purpose:
Our goal was to evaluate whether systemic administration of NV1042, an interleukin-12 (IL-12)-expressing oncolytic herpes simplex virus, and its noncytokine parental vector NV1023 are effective against preexisting metastatic prostate cancer in an immunocompetent mice model.
Experimental Design:
Metastatic TRAMP-C2 lung tumors established in C57Bl/6 or nude mice were treated on day 21 with four i.v. administrations of NV1042 or NV1023 and sacrificed on day 42 to assess virus efficacy and the potential mechanism of efficacy.
Results:
NV1042 or NV1023 treatment was similarly effective in eliminating extrapleural and hemorrhagic tumors present in mock-treated mice. However, NV1042 was further effective compared with NV1023 in controlling the growth of lung tumors (as determined by mean surface tumor nodule number, lung weights, and surface tumor burden) and in extending survival. NV1042-treated mice exhibited a transient increase of serum IL-12 1 day posttreatment, whereas IL-12 levels in tumor bearing lungs persisted a further 2 days at least. Only splenocytes from NV1042-treated mice secreted IFN-gamma in response to TRAMP-C2 stimulation and displayed natural killer activity. The IL-12-mediated enhancement observed with NV1042 in the syngeneic model was abrogated in athymic mice treated in a similar manner, thus indicating a role for T cells in the augmented efficacy of NV1042 virus.
Conclusions:
Systemic administration of the IL-12-expressing NV1042 virus is more effective than its noncytokine parent, NV1023, against preestablished metastatic lung tumors. Given the clinical safety profile of NV1020, the parental vector of NV1023, and NV1042's enhanced efficacy and ability to activate the host immune system, NV1042 merits clinical consideration for treating metastatic prostate cancers.
Insights
The interleukin-12 (IL-12)-expressing oncolytic herpes simplex virus NV1042 effectively controlled metastatic prostate cancer in mice. NV1042 demonstrated superior efficacy over its parent vector NV1023 in reducing lung tumors and extending survival.
Area of Science:
- Oncolytic virotherapy
- Immunotherapy
- Prostate cancer research
Background:
- Metastatic prostate cancer remains a significant clinical challenge.
- Oncolytic viruses engineered to express cytokines offer a promising therapeutic strategy.
- Interleukin-12 (IL-12) is a key cytokine for activating anti-tumor immune responses.
Purpose of the Study:
- To evaluate the efficacy of NV1042, an IL-12-expressing oncolytic herpes simplex virus, against pre-existing metastatic prostate cancer in immunocompetent mice.
- To compare the therapeutic effects of NV1042 with its non-cytokine parental vector, NV1023.
Main Methods:
- Metastatic TRAMP-C2 prostate cancer lung tumors were established in C57Bl/6 mice.
- Mice received four intravenous administrations of NV1042 or NV1023 on day 21.
- Tumor burden, survival, and immune responses were assessed on day 42.
Main Results:
- Both NV1042 and NV1023 reduced extrapleural and hemorrhagic tumors.
- NV1042 significantly outperformed NV1023 in controlling lung tumor growth and extending survival.
- NV1042 induced transient serum IL-12, sustained lung IL-12, and activated splenocyte IFN-gamma secretion and NK activity, dependent on T cells.
Conclusions:
- Systemic administration of NV1042 is more effective than NV1023 against established metastatic lung tumors.
- NV1042's enhanced efficacy and immune activation warrant clinical investigation for metastatic prostate cancer.
- The parental vector NV1020 has a known clinical safety profile, supporting the potential translation of NV1042.
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