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Table 1 Murine cancer vaccine studies that utilized MDSC inhibitors

From: Myeloid derived suppressor cells – a new therapeutic target in the treatment of cancer

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

  1. 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.