Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial

2012 ◽  
Vol 13 (5) ◽  
pp. 509-517 ◽  
Author(s):  
Alfons JM van den Eertwegh ◽  
Jurjen Versluis ◽  
H Pieter van den Berg ◽  
Saskia JAM Santegoets ◽  
R Jeroen A van Moorselaar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase 1 ◽  
Colony Stimulating Factor ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Castration Resistant ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Combined Immunotherapy

scholarly journals Inhibition of TAMs improves the response to docetaxel in castration-resistant prostate cancer

2019 ◽  
Vol 26 (1) ◽  
pp. 131-140 ◽  
Author(s):  
Wei Guan ◽  
Junhui Hu ◽  
Lu Yang ◽  
Ping Tan ◽  
Zhuang Tang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Receptor Kinase ◽  
Castration Resistant Prostate Cancer ◽  
Small Molecule Antagonist ◽  
Castration Resistant ◽  
Docetaxel Treatment ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Receptor Kinase Signaling ◽  
Stimulating Factor

For men with castration-resistant prostate cancer (CRPC), androgen-deprivation therapy (ADT) often becomes ineffective requiring the addition of docetaxel, a proven effective chemotherapy option. Tumor-associated macrophages (TAMs) are known to provide protumorigenic influences that contribute to treatment failure. In this study, we examined the contribution of TAMs to docetaxel treatment. An increased infiltration of macrophages in CRPC tumors was observed after treatment with docetaxel. Prostate cancer cells treated with docetaxel released more macrophage colony-stimulating factor (M-CSF-1 or CSF-1), IL-10 and other factors, which can recruit and modulate circulating monocytes to promote their protumorigenic functions. Inhibition of CSF-1 receptor kinase signaling with a small molecule antagonist (PLX3397) in CRPC models significantly reduces the infiltration of TAMs and their influences. As such, the addition of PLX3397 to docetaxel treatment resulted in a more durable tumor growth suppression than docetaxel alone. This study reveals a rational strategy to abrogate the influences of TAMs and extend the treatment response to docetaxel in CRPC.

scholarly journals Phase 1 study of lenzilumab, a recombinant anti–human GM-CSF antibody, for chronic myelomonocytic leukemia

Blood ◽  
2020 ◽  
Vol 136 (7) ◽  
pp. 909-913 ◽  
Author(s):  
Mrinal M. Patnaik ◽  
David A. Sallman ◽  
Abhishek A. Mangaonkar ◽  
Rachel Heuer ◽  
Jeffery Hirvela ◽  
...  
Keyword(s):  
Preliminary Data ◽  
Phase 1 ◽  
Chronic Myelomonocytic Leukemia ◽  
Colony Stimulating Factor ◽  
Phase 1 Study ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Myelomonocytic Leukemia ◽  
Stimulating Factor

In this phase 1 trial, inhibition of granulocyte-macrophage colony-stimulating factor (GM-CSF) was associated with clinically meaningful responses in 5 of 15 patients with relapsed or refractory chronic myelomonocytic leukemia (CMML). Preliminary data suggest that this approach may be tractable in CMML bearing activating NRAS mutations.

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