On Safety and Efficacy

1:  ΔPK eradicates cancer stem cells (CSCs),1 which are thought to be a cause of metastasis.2  If this action is confirmed in clinical trials, this will be a paradigm change in cancer treatment.2

HSV-2 have been shown to destroy tumor cells in breast,15, 3 lung4, head/neck5, pancreatic6, renal7, prostate8, brain9, ovarian10 and malignant melanoma.15, 11

  1. ΔPK showed complete eradication of malignant melanoma in an animal model – showing no remaining cancer stem cells.15
  2. ΔPK has been injected at 106 pfu in 16 human subjects showing no side effects greater than placebo12 and no severe side effects. In addition safe in intracranially13 and intraperitoneally14 injected animals15

The safety and efficacy of ΔPK in animal and cell models are superior to any other oncolytic virus.

1  Calpain-dependent clearance of the autophagy protein p62/SQSTM1 is a contributor to ΔPK oncolytic activity in melanoma.  Colunga A, Bollino D, Schech A, Aurelian L.  Gene Ther. 2014 Apr;21(4):371-8.

2  CD44 splice isoform switching determines breast cancer stem cell state.  Zhang H, Brown RL, Wei Y, Zhao P, Liu S, Liu X, Deng Y, Hu X, Zhang J, Gao XD, Kang Y, Mercurio AM, Goel HL, Cheng C.  Genes Dev. 2019 Feb 1;33(3-4):166-179

Apoptotic death of cancer stem cells for cancer therapy. He YC et al. Int J Mol Sci. 2014 May 12;15(5):8335-51

3  A mutant type 2 herpes simplex virus deleted for the protein kinase domain of the ICP10 gene is a potent oncolytic virus. Fu X, Tao L, Cai R, Prigge J, Zhang X.Mol Ther. 2006 May;13(5):882-90. Epub 2006 Mar 29.

4  Coadministration of a herpes simplex virus-2 based oncolytic virus and cyclophosphamide produces a synergistic antitumor effect and enhances tumor-specific immune responses.Li H, Zeng Z, Fu X, Zhang X.Cancer Res. 2007 Aug 15;67(16):7850-5.

5  An HSV-2-based oncolytic virus deleted in the PK domain of the ICP10 gene is a potent inducer of apoptotic death in tumor cells.Fu X, Tao L, Zhang X.Gene Ther. 2007 Aug;14(16):1218-25. Epub 2007 May 31.

6  Effective treatment of pancreatic cancer xenografts with a conditionally replicating virus derived from type 2 herpes simplex virus.Fu X, Tao L, Li M, Fisher WE, Zhang X.Clin Cancer Res. 2006 May 15;12(10):3152-7.

7  Antitumor effects of two newly constructed oncolytic herpes simplex viruses against renal cell carcinoma. Fu X, Nakamori M, Tao L, Amato R, Zhang X.Int J Oncol. 2007 Jun;30(6):1561-7.

8  Potent antitumor activity after systemic delivery of a doubly fusogenic oncolytic herpes simplex virus against metastatic prostate cancer.  Nakamori M, Fu X, Pettaway CA, Zhang X.  Prostate. 2004 Jun 15;60(1):53-60

9  Virotherapy with a type 2 herpes simplex virus-derived oncolytic virus induces potent antitumor immunity against neuroblastoma.Li H, Dutuor A, Tao L, Fu X, Zhang X.Clin Cancer Res. 2007 Jan 1;13(1):316-22.

10  An oncolytic virus derived from type 2 herpes simplex virus has potent therapeutic effect against metastatic ovarian cancer.  Fu X, Tao L, Zhang X.Cancer Gene Ther. 2007 May;14(5):480-7. Epub 2007 Feb 9.

11  A mutant type 2 herpes simplex virus deleted for the protein kinase domain of the ICP10 gene is a potent oncolytic virus. Fu X, Tao L, Cai R, Prigge J, Zhang X.Mol Ther. 2006 May;13(5):882-90. Epub 2006 Mar 29. (Breast cell line erroneously identified and is in fact melanoma according to ATCC)

12  A double-blind study of the efficacy and safety of the ICP10deltaPK vaccine against recurrent genital HSV-2 infections.  Casanova G1, Cancela R, Alonzo L, Benuto R, Magana Mdel C, Hurley DR, Fishbein E, Lara C, Gonzalez T, Ponce R, Burnett JW, Calton GJ.    Cutis. 2002 Oct;70(4):235-9.

13  The HSV-2 protein ICP10PK prevents neuronal apoptosis and loss of function in an in vivo model of neurodegeneration associated with glutamate excitotoxicity. Golembewski EK, Wales SQ, Aurelian L, Yarowsky PJ.   Exp Neurol. 2007;203(2):381–93.

14  Intranasal administration of the growth-compromised HSV-2 vector DeltaRR prevents kainate-induced seizures and neuronal loss in rats and mice. Laing JM, Gober MD, Golembewski EK, Thompson SM, Gyure KA, Yarowsky PJ, Aurelian L.  Mol Ther. 2006;13(5):870–81.

15  The HSV-2 mutant DeltaPK induces melanoma oncolysis through nonredundant death programs and associated with autophagy and pyroptosis proteins.  Colunga AG, Laing JM, Aurelian L Gene Ther. 2010 Mar; 17(3):315-27.