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The Oncologist, Vol. 12, No. suppl_2, 22-26, October 2007; doi:10.1634/theoncologist.12-S2-22
© 2007 AlphaMed Press

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The Role of Sargramostim (rhGM-CSF) as Immunotherapy

Edmund K. Waller

Bone Marrow and Stem Cell Transplant Center, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA

Key Words. Granuloctye-macrophage colony-stimulating factor • Cancer vaccines • Immunotherapy • Dendritic cells

Correspondence: Edmund K. Waller, M.D., Ph.D., Bone Marrow and Stem Cell Transplant Center, Winship Cancer Institute, Emory University, 1365-C Clifton Road NE, Atlanta, Georgia 30322, USA. Telephone: 404-727-4995; Fax: 404-712-9995; e-mail: ewaller{at}emory.edu

Disclosure: E.K.W. has acted as a consultant to Berlex.

GM-CSF stimulates the differentiation of hematopoietic progenitors to monocytes and neutrophils, and reduces the risk for febrile neutropenia in cancer patients. GM-CSF also has been shown to induce the differentiation of myeloid dendritic cells (DCs) that promote the development of T-helper type 1 (cellular) immune responses in cognate T cells. This review summarizes some of the immunological effects of GM-CSF relevant to antitumor immunity in cancer patients. GM-CSF has been used to augment the activity of rituximab in patients with follicular lymphoma and to induce autologous antitumor immunity in patients with hormone-refractory prostate cancer. GM-CSF causes upregulation of costimulatory molecule expression on leukemia blasts in vitro, enhancing their ability to present antigen to allogeneic T cells, and, in combination with interferon-{alpha}, can induce antitumor immune responses in patients whose acute leukemia has relapsed following allogeneic hematopoietic progenitor cell transplant. Tumor cells engineered to secrete GM-CSF are particularly effective as antitumor vaccines, and the addition of GM-CSF to standard vaccines may increase their effectiveness by recruiting DCs to the site of vaccination. However, a significant limitation in the use of GM-CSF as an immunostimulatory agent is that objective antitumor responses are infrequent, and are often not durable. Effective and durable antitumor immunity will likely require novel methods to eliminate counterregulatory immune responses that limit activation and expansion of cytotoxic T cells with antitumor activity.




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L. de la Cruz-Merino, E. Grande-Pulido, A. Albero-Tamarit, and M. E. Codes-Manuel de Villena
Cancer and Immune Response: Old and New Evidence for Future Challenges
Oncologist, December 1, 2008; 13(12): 1246 - 1254.
[Abstract] [Full Text] [PDF]


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