AB Vector - GM-CSF applications in research and medicine

  GM-CSF applications in research and medicine
 
  GM-CSF is a growth factor that stimulates generation of granulocytes, macrophages, and dendritic cells from hematopoietic progenitor cells. It also enhances the activity of a range of mature hematopoietic cell functions, including mature cell survival, phagocytosis, leukocyte adhesion, and proliferation and activation of macrophages1. The human and murine molecules are species specific and exhibit no cross-species reactivity.

In a research laboratory human GM-CSF can be used for a variety of applications including cultivation of hematopoietic progenitor cells from human bone marrow, in vitro generation of monocyte-derived dendritic cells (e.g. together with IL-4), in vitro differentiation of CD34+ cells towards eosinophils, migration assays for eosinophils.

In medicine GM-CSF (Molgramostin, Sagramostin) is used to treat neutropenia in cancer patients undergoing chemotherapy, in AIDS patients during therapy, and in patients after bone marrow transplantation. An important aspect of its clinical utility is allowing the delivery of planned anti-cancer therapy on schedule, which otherwise could be compromised because of neutropenia2. Therefore, dose-dense chemotherapy has become feasible3.

GM-CSF showed excellent efficacy in treatment of chronic skin ulcers, wounds and burns4-9. Unfortunately, high treatment costs preclude its wide application for these purposes. Treatment of mucosal ulcers in inflammatory bowel disease (IBD, colitis, Crohn’s disease) is under evaluation10,11. GM-CSF was also demonstrated to potentiate an immune response when co-administered at vaccinations, non-responders included, and immunotherapeutic action was significantly enhanced as a result of GM-CSF being coadministered12-17.

References:

1. Conti L, Gessani S. GM-CSF in the generation of dendritic cells from human blood monocyte precursors: recent advances. Immunobiology, 213(9-10):859-70, 2008.

2. Dale DC. Advances in the treatment of neutropenia. Curr Opin Support Palliat Care, 3(3):207-12, 2009.

3. Heuser et al. Use of colony-stimulating factors for chemotherapy-associated neutropenia: review of current guidelines. Semin Hematol, 44(3):148-56, 2007.

4. Jaschke et al. Recombinant human granulocyte-macrophage colony-stimulating factor applied locally in low doses enhances healing and prevents recurrence of chronic venous ulcers. Int J Dermatol, 38(5):380-6, 1999.

5. Cianfarani et al. Granulocyte/macrophage colony-stimulating factor treatment of human chronic ulcers promotes angiogenesis associated with de novo vascular endothelial growth factor transcription in the ulcer bed. Br J Dermatol, 154(1):34-41, 2006.

6. Groves RW, Schmidt-Lucke JA. Recombinant human GM-CSF in the treatment of poorly healing wounds. Adv Skin Wound Care, 13(3 Pt 1):107-12, 2000.

7. Mann et al. Granulocyte-macrophage colony-stimulating factor is essential for normal wound healing. J Investig Dermatol Symp Proc, 11(1):87-92, 2006.

8. Meier K, Nanney LB. Emerging new drugs for wound repair. Expert Opin Emerg Drugs, 11(1):23-37, 2006.

9. Wang et al. Effect of recombinant human granulocyte-macrophage colony stimulating factor on wound healing in patients with deep partial thickness burn. Zhonghua Shao Shang Za Zhi, 24(2):107-10, 2008.

10. Barahona-Garrido J, Yamamoto-Furusho JK. New treatment options in the management of IBD - focus on colony stimulating factors. Biologics, 2(3):501-4, 2008.

11. Guidi et al. Treatment of Crohn's disease with colony-stimulating factors: An overview. Ther Clin Risk Manag, 4(5):927-34, 2008.

12. Sasaki et al. Efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant for hepatitis B virus in patients with HIV infection. Vaccine, 21(31):4545-9, 2003.

13. Cruciani et al. Granulocyte macrophage colony-stimulating factor as an adjuvant for hepatitis B vaccination: a meta-analysis. Vaccine, 25(4):709-18, 2007.

14. Lin et al. Immune effects of three different programs for revaccination among adults of non- and hypo-responders to hepatitis B vaccine. Zhonghua Yu Fang Yi Xue Za Zhi, 43(1):37-40, 2009.

15. Fong et al. Potentiating endogenous antitumor immunity to prostate cancer through combination immunotherapy with CTLA4 blockade and GM-CSF. Cancer Res, 69(2):609-15, 2009.

16 Harzstark AL, Small EJ.. Immunotherapeutics in development for prostate cancer. Oncologist,14(4):391-8, 2009.

17 Ferrajoli A. Incorporating the use of GM-CSF in the treatment of chronic lymphocytic leukemia. Leuk Lymphoma, 50(3):514-6, 2009.