Summary of Emerging Applications of rHuGM-CSF
| Therapeutic Use . | Preclinical Actions of rHuGM-CSF . | References . | Clinical Results With rHuGM-CSF . | References . |
|---|---|---|---|---|
| Fungal infections | Increases receptor expression on macrophages. Enhances fungicidal activity againstAspergillus fumigatus, Candida albicans, Cryptococcus neoformans, Histoplasma capsulatum, Torulopsis glabrata. Counteracts dexamethasone-induced inhibition of superoxide anion release by monocytes. | 16, 88, 92-95, 98-102 | Decreases incidence of fungal infections versus placebo in AuBMT patients. Reduces mortality due to fungal infections in elderly patients with AML. As an adjunct to amphotericin B, improves recovery from Candida andAspergillus infections. Improves oropharyngeal candidiasis refractory to fluconazole in HIV-infected patients. | 112-116 |
| HIV infection and its complications | Suppresses HIV expression. Enhances antiretroviral activity of zidovudine and stavudine. Downregulates expression of CCR5, reducing the susceptibility of macrophages to HIV infection. Promotes killing of Mycobacterium avium-intracellular(MAC). | 105, 107, 124-129 | Increases CD4 count. Decreases viral load. As adjunctive treatment of MAC, reduces the number of viable intracellular MAC/mL. | 136, 137, 139 |
| Vaccine adjuvant | Increases class II MHC expression and stimulates T-cell immune responses. Augments the primary in vitro immune response to sheep red blood cells by murine spleen cells. Enhances expression of costimulatory molecules and adhesion molecules and enhances production of other cytokines. Primes T cells for IL-2–induced proliferation. Augments LAK cell generation in conjunction with IL-2. | 12, 14, 15, 142-145 | Enhances antibody response to hepatitis B vaccine. Increases the percent of patients who seroconverted to all three strains of flu vaccine. | 141, 146, 147 |
| Antitumor therapy | Enhances monocyte cytotoxicity against human tumor cells. Enhances IL-2–mediated LAK cell function. Increases secretion of matrix metalloelastase with subsequent production of angiostatin. Facilitates tumor antigen presentation. | 56, 149-153 | Prolongs disease-free survival and overall survival compared with historical controls in patients with advanced melanoma. Of 20 stage IV melanoma patients who received sargramostim as an adjuvant to a melanoma vaccine, 4 had partial to complete responses. | 155-157 |
| Immunotherapy for AML | Enhances activated killer cell function. Upregulates expression of intercellular adhesion molecule-1 and lymphocyte function associated molecules. | 160, 161 | Decreases risk of relapse compared with controls (37.4% v 49.5%). | 160 |
| Mucositis, stomatitis, diarrhea | Stimulates the migration and proliferation of endothelial cells and promotes keratinocyte growth. | 162, 163 | Reduces incidence and severity of mucositis in patients with sarcoma, advanced head and neck cancer, and those undergoing allogeneic BMT. Shortens the duration of mucositis in children undergoing stem cell transplant. Decreases rates of diarrhea in colorectal cancer patients receiving 5-FU. | 164-168, 170 |
| Wound healing | Increases formation of granulation tissue. Increases breaking strength of incisional wounds. Decreases time to wound healing. | 171-173 | Intradermal injections of rHuGM-CSF results in enlarged keratinocytes, keratinocyte proliferation, thickening of the epidermis, accumulation of Langerhans cells, and enhances healing. Reduces mean ulcer surface area versus saline in patients with chronic leg ulcers. | 174-180 |
| Therapeutic Use . | Preclinical Actions of rHuGM-CSF . | References . | Clinical Results With rHuGM-CSF . | References . |
|---|---|---|---|---|
| Fungal infections | Increases receptor expression on macrophages. Enhances fungicidal activity againstAspergillus fumigatus, Candida albicans, Cryptococcus neoformans, Histoplasma capsulatum, Torulopsis glabrata. Counteracts dexamethasone-induced inhibition of superoxide anion release by monocytes. | 16, 88, 92-95, 98-102 | Decreases incidence of fungal infections versus placebo in AuBMT patients. Reduces mortality due to fungal infections in elderly patients with AML. As an adjunct to amphotericin B, improves recovery from Candida andAspergillus infections. Improves oropharyngeal candidiasis refractory to fluconazole in HIV-infected patients. | 112-116 |
| HIV infection and its complications | Suppresses HIV expression. Enhances antiretroviral activity of zidovudine and stavudine. Downregulates expression of CCR5, reducing the susceptibility of macrophages to HIV infection. Promotes killing of Mycobacterium avium-intracellular(MAC). | 105, 107, 124-129 | Increases CD4 count. Decreases viral load. As adjunctive treatment of MAC, reduces the number of viable intracellular MAC/mL. | 136, 137, 139 |
| Vaccine adjuvant | Increases class II MHC expression and stimulates T-cell immune responses. Augments the primary in vitro immune response to sheep red blood cells by murine spleen cells. Enhances expression of costimulatory molecules and adhesion molecules and enhances production of other cytokines. Primes T cells for IL-2–induced proliferation. Augments LAK cell generation in conjunction with IL-2. | 12, 14, 15, 142-145 | Enhances antibody response to hepatitis B vaccine. Increases the percent of patients who seroconverted to all three strains of flu vaccine. | 141, 146, 147 |
| Antitumor therapy | Enhances monocyte cytotoxicity against human tumor cells. Enhances IL-2–mediated LAK cell function. Increases secretion of matrix metalloelastase with subsequent production of angiostatin. Facilitates tumor antigen presentation. | 56, 149-153 | Prolongs disease-free survival and overall survival compared with historical controls in patients with advanced melanoma. Of 20 stage IV melanoma patients who received sargramostim as an adjuvant to a melanoma vaccine, 4 had partial to complete responses. | 155-157 |
| Immunotherapy for AML | Enhances activated killer cell function. Upregulates expression of intercellular adhesion molecule-1 and lymphocyte function associated molecules. | 160, 161 | Decreases risk of relapse compared with controls (37.4% v 49.5%). | 160 |
| Mucositis, stomatitis, diarrhea | Stimulates the migration and proliferation of endothelial cells and promotes keratinocyte growth. | 162, 163 | Reduces incidence and severity of mucositis in patients with sarcoma, advanced head and neck cancer, and those undergoing allogeneic BMT. Shortens the duration of mucositis in children undergoing stem cell transplant. Decreases rates of diarrhea in colorectal cancer patients receiving 5-FU. | 164-168, 170 |
| Wound healing | Increases formation of granulation tissue. Increases breaking strength of incisional wounds. Decreases time to wound healing. | 171-173 | Intradermal injections of rHuGM-CSF results in enlarged keratinocytes, keratinocyte proliferation, thickening of the epidermis, accumulation of Langerhans cells, and enhances healing. Reduces mean ulcer surface area versus saline in patients with chronic leg ulcers. | 174-180 |
Abbreviations: CCR5, β-chemokine receptor on macrophages; MHC, major histocompatibility complex; LAK, lymphokine-activated killer; 5-FU, fluorouracil.