Murine cancer vaccine studies that utilized MDSC inhibitors
| MDSC Inhibition Strategy | Tumor model | Vaccine | Effect of MDSC Modulation |
|---|---|---|---|
| ATRA [14] | (a) C3 fibrosarcoma in C57BL/6 mice | (a) H-2Db-restricted epitope of the HPV-16 E7 | (a) Decreased tumor size by ~3 fold at 35 days; enhanced CD8+ response |
| (b) 3-methylcholanthrene-induced sarcoma containing mutant p53 gene in BALB/c mice | (b) Wild type p53 DC vaccine | (b) Decreased tumor size by ~5 fold; enhanced CD8+ responses | |
| Gemcitabine [15] | Pancreas adenocarcinoma (Panc02) expressing murine survivin in C57BL/6 mice | Modified Vaccinia Ankara virus (MVA) expressing murine survivin protein | 50% survival vs. 0% in control mice at 50 days; enhanced CD8+ responses |
| ATRA + anti-CD25 antibody [16] | Tumor bearing IL-1RI competent or IL-1RI deficient mice | cDNA IL-1α attenuated S. typhimurium and/or IL-1 competent or IL-1 deficient fibrosarcoma cell lysates | Decreased MDSC and Treg levels; significantly enhanced survival of IL-1 RI competent mice |
| Nitroaspirin derivative (NCX-4016) [17] | (a) CT26 colon carcinoma in C57BL/6 and BALB/c mice | Plasmid DNA vaccine encoding extracellular and trans-membrane domains of p185 peptide | (a) 20% cure rate at 120 days |
| (b) Her-2/neu + (p185) N2C breast carcinoma in C57BL/6 and BALB/c mice | (b) 56% cure rate at 120 days | ||
| CDDO-Me (Triterpenoid) [18] | EL-4 thymoma in C57BL/6 | DC transduced with murine survivin | Decreased tumor size by 2 fold; enhanced antigen specific immune response |
| IL-13-PE (cytotoxin composed of IL-13 and Pseudomonas exotoxin) [19] | (a) 4 T1 breast carcinoma in BALB/c mice | DNA vaccine encoding α2 chain of IL-13R | Decreased tumor size by 5 fold; decreased MDSC and Treg levels; enhanced T cell responses; enhanced survival by 35 days. |
| (b) MCA304 sarcoma in C57BL/6 mice | |||
| Sunitinib [20] | MO5 (B16.OVA: H-2b) melanoma on C57BL/6 mice | IL-12 transfected DC pulsed with OVA I and II peptides. | Loss of tumor associated MDSC and Tregs; enhanced CD8+ T cell responses |
| Gemcitabine [21] | Her-2/neu + SK-BR-3 breast carcinoma or mHER2/CT26 (colon carcinoma transfected with murine Her-2/neu) in BALB/c mice | (a) AdhHM | (a) No anti-tumor effect of AdhHM alone |
| (b) AdhHM + anti- GITR antibody | (b) Decreased tumor size by >5 fold; (p < 0.005); CD8+ cell dependent rejection of syngeneic tumor cells | ||
| (c) AdhHM + α galactosylceramide loaded DCs | (c) Decreased tumor size by >5 fold | ||
| Cisplatin [22] | TC-1 lung carcinoma expressing E7 protein in C57BL/6 mice | E7 DNA vaccine | Enhanced tumor lysis mediated by E7 specific CD8+ cells; reduced tumor volume |
| Zoledronic Acid [23] | Transgenic Balb T-Neu mice (express activated rat c-erbB-2/neu transgene) | Plasmid DNA encoding portion of the rat p185/Her-2 gene | Delayed tumor onset and reduced in tumor size |
Abbreviations: ATRA – All-Trans Retinoic Acid, AdhHM - Adenoviral vector expressing xenogenic human Her-2/neu, DC – Dendritic Cell, GITR - Glucocorticoid Induced Tumor Necrosis Factor Receptor Family- Related Receptor.