Immunologic Approaches for Oncolytic Viral Therapy of Prostate Cancer
Annual rept. 1 Feb 2004-31 Jan 2005
MASSACHUSETTS GENERAL HOSPITAL BOSTON
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Replication competent oncolytic herpes simplex viruses HSV exert a dual effect by their direct cytocidal action and by eliciting tumor specific immunity. These viruses can also deliver immunoregulatory molecules to tumors so as to enhance the cumulative antitumor response. This is particularly desirable for prostate cancers, which are usually poorly immunogenic. In order to generate a cytokine expressing oncolytic virus with enhanced cytotoxicity against prostate cancers and which can stimulate the immune system so as to overcome the immunological complacency observed in prostate cancer patients, we are genetically engineering PC-IL 12 virus using BAC technology from the PC virus, which is an HSV 1 strain selected by screening for enhanced cytotoxicity against prostate cancer cells. The construction is progressing successfully. Additionally, we have described in this report that an IL-12 expressing oncolytic virus NV1042 is superior to a GM-CSF expressing virus or a non-cytokine virus in its efficacy against both MHC class I positive Prl4-2 and negative TRAMP-C2 mouse prostate tumors. The NV 1042 treated tumors exhibited increased immune cell infiltration and decreased levels of angiogenesis. Thus, an IL-12 expressing oncolytic herpes virus is an effective therapeutic vector against prostate cancers irrespective of their MHC class I status.
- Medicine and Medical Research