HER2 Support Group Forums - View Single Post - GM-CSF as therapy

Rich66 · 11-14-2009, 01:07 AM

Ann Surg Oncol. 2009 Nov 14. [Epub ahead of print]
Local and Distant Immunity Induced by Intralesional Vaccination with an Oncolytic Herpes Virus Encoding GM-CSF in Patients with Stage IIIc and IV Melanoma.

Kaufman HL, Kim DW, Deraffele G, Mitcham J, Coffin RS, Kim-Schulze S.
Department of Surgery, Medicine and Immunology, Rush University Medical Center, Chicago, IL, USA, Howard_L_Kaufman@rush.edu.
BACKGROUND: An oncolytic herpes simplex virus engineered to replicate selectively in tumor cells and to express granulocyte-macrophage colony-stimulating factor (GM-CSF) was tested as a direct intralesional vaccination in melanoma patients. The work reported herein was performed to better characterize the effect of vaccination on local and distant antitumor immunity. METHODS: Metastatic melanoma patients with accessible lesions were enrolled in a multicenter 50-patient phase II clinical trial of an oncolytic herpesvirus encoding GM-CSF (Oncovex(GM-CSF)). An initial priming dose of 10(6) pfu vaccine was given by intratumoral injection, followed by 10(8) pfu every 2 weeks to 24 total doses. Peripheral blood and tumor tissue were collected for analysis of effector T cells, CD4(+)FoxP3(+) regulatory T cells (Treg), CD8(+)FoxP3(+) suppressor T cells (Ts), and myeloid-derived suppressive cells (MDSC). RESULTS: Phenotypic analysis of T cells derived from tumor samples suggested distinct differences from peripheral blood T cells. There was an increase in melanoma-associated antigen recognized by T cells (MART-1)-specific T cells in tumors undergoing regression after vaccination compared with T cells derived from melanoma patients not treated with vaccine. There was also a significant decrease in Treg and Ts cells in injected lesions compared with noninjected lesions in the same and different melanoma patients. Similarly MDSC were increased in melanoma lesions but underwent a significant decrease only in vaccinated lesions. CONCLUSIONS: Melanoma patients present with elevated levels of Tregs, Ts, and MDSC within established tumors. Direct injection of Oncovex(GM-CSF) induces local and systemic antigen-specific T cell responses and decreases Treg, Ts, and MDSC in patients exhibiting therapeutic responses.

PMID: 19915919 [PubMed - as supplied by publisher]

What is OncoVEXGM-CSF?

OncoVEXGM-CSF is a novel biologic drug that is a combined

oncolytic virus (a reprogrammed virus that has been converted into a cancer-fighting agent that attacks cancerous cells, while leaving healthy cells undamaged)

and

vaccine (a biological preparation that establishes or improves immunity to a particular disease) approach to treating advance melanoma.

The oncolytic virus component is a special strain of herpes simplex type 1 (HSV-1) virus that has been reprogrammed to infect only cancer cells. So the OncoVEXGM-CSF virus is disabled in its ability to infect normal healthy cells. The immune boosting component is the human GM-CSF gene that is put into the genetic material of the HSV-1 virus. OncoVEXGM-CSF is injected every 2 weeks into melanoma sites on the skin, just under the skin (subcutaneous) or other tumor locations that can be reached by injecting through the skin (such as lymph nodes).
GM-CSF is the name of the "control" drug that may be given to you if you take part in this research study. GM-CSF has been used in studies with patients with melanoma, but it has not been approved by the FDA for this use.

11-14-2009, 01:07 AM	#7
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	Re: GM-CSF as therapy Ann Surg Oncol. 2009 Nov 14. [Epub ahead of print] Local and Distant Immunity Induced by Intralesional Vaccination with an Oncolytic Herpes Virus Encoding GM-CSF in Patients with Stage IIIc and IV Melanoma. Kaufman HL, Kim DW, Deraffele G, Mitcham J, Coffin RS, Kim-Schulze S. Department of Surgery, Medicine and Immunology, Rush University Medical Center, Chicago, IL, USA, Howard_L_Kaufman@rush.edu. BACKGROUND: An oncolytic herpes simplex virus engineered to replicate selectively in tumor cells and to express granulocyte-macrophage colony-stimulating factor (GM-CSF) was tested as a direct intralesional vaccination in melanoma patients. The work reported herein was performed to better characterize the effect of vaccination on local and distant antitumor immunity. METHODS: Metastatic melanoma patients with accessible lesions were enrolled in a multicenter 50-patient phase II clinical trial of an oncolytic herpesvirus encoding GM-CSF (Oncovex(GM-CSF)). An initial priming dose of 10(6) pfu vaccine was given by intratumoral injection, followed by 10(8) pfu every 2 weeks to 24 total doses. Peripheral blood and tumor tissue were collected for analysis of effector T cells, CD4(+)FoxP3(+) regulatory T cells (Treg), CD8(+)FoxP3(+) suppressor T cells (Ts), and myeloid-derived suppressive cells (MDSC). RESULTS: Phenotypic analysis of T cells derived from tumor samples suggested distinct differences from peripheral blood T cells. There was an increase in melanoma-associated antigen recognized by T cells (MART-1)-specific T cells in tumors undergoing regression after vaccination compared with T cells derived from melanoma patients not treated with vaccine. There was also a significant decrease in Treg and Ts cells in injected lesions compared with noninjected lesions in the same and different melanoma patients. Similarly MDSC were increased in melanoma lesions but underwent a significant decrease only in vaccinated lesions. CONCLUSIONS: Melanoma patients present with elevated levels of Tregs, Ts, and MDSC within established tumors. Direct injection of Oncovex(GM-CSF) induces local and systemic antigen-specific T cell responses and decreases Treg, Ts, and MDSC in patients exhibiting therapeutic responses. PMID: 19915919 [PubMed - as supplied by publisher] What is OncoVEXGM-CSF? OncoVEXGM-CSF is a novel biologic drug that is a combined oncolytic virus (a reprogrammed virus that has been converted into a cancer-fighting agent that attacks cancerous cells, while leaving healthy cells undamaged) and vaccine (a biological preparation that establishes or improves immunity to a particular disease) approach to treating advance melanoma. The oncolytic virus component is a special strain of herpes simplex type 1 (HSV-1) virus that has been reprogrammed to infect only cancer cells. So the OncoVEXGM-CSF virus is disabled in its ability to infect normal healthy cells. The immune boosting component is the human GM-CSF gene that is put into the genetic material of the HSV-1 virus. OncoVEXGM-CSF is injected every 2 weeks into melanoma sites on the skin, just under the skin (subcutaneous) or other tumor locations that can be reached by injecting through the skin (such as lymph nodes). GM-CSF is the name of the "control" drug that may be given to you if you take part in this research study. GM-CSF has been used in studies with patients with melanoma, but it has not been approved by the FDA for this use. __________________ Mom's treatment history (link)