Table 1.
Previously published works into the role of S100A8, S100A9 or heterodimer S100A8/A9 in cancer.
| Ref | Blocking strategy | In vivo model | Readout and findings |
|---|---|---|---|
| (8) | mAbGB3.1 anti-glycan Ab against RAGE, treatment started after removal of primary tumor | BALB/c, DO11.10, 4T1 mammary carcinoma, | Targeting caused reduced frequency of Gr1+ cells in spleen and lymph nodes, no reduction of T cell suppression per cell. Tumor growth effect not investigated. |
| (9) | S100A9KO mice and overexpression of S100A8, S100A9 and S100A8/A9 in embryonic stem cells, transgenic mice with overexpression of S100A9. | EL-4 lymphoma, C3 sarcoma, CFA injection | Reduced tumor growth, frequency of myeloid subsets in spleen and differentiation of stem cells into DCs. Reduced differentiation to suppressive myeloid cells vivo and reduced T cell suppression activity. |
| (21) | Tasquinimod (oral treatment, day 0 or 1 to end of experiment), q-compound targeting TLR4 signaling of S100A9, alone, with SurVaxM peptide and GM-CSF or with tumor-targeted superantigen. | Myc-CaP and B16-h5T4 cell lines, | Reduced tumor growth by combination therapies. Reduced frequency of myeloid subsets in spleen, tumor and blood, and some reduction in T cell suppression by targeting. |
| (32) | Tasquinimod (oral treatment twice daily) alone or in combination with anti-PD-L1 | Bladder cancer: AY-27 in rats, MBT-2 in C3H/HeNRj mice | Reduced tumor growth by single treatment when given early. Effective in TLR4-defective mice. No change frequencies of myeloid or lymphoid immune cells in tumor but change towards an M1/antitumor phenotype. Synergistic effect when combined with CPI. |
| (33) | Eritoran, and antagonist of TLR4/MD-2 complex. 5 days treatment. | LLC lung carcinoma | Reduced tumor growth and pulmonary recruitment of myeloid cells. |
| (34) | Neutralizing antibody against S100A8/A9, Ab45 | Metastatic melanoma | Treatment reduced lung tropic melanoma metastasis |
| (35) | S100A8 competitive inhibitory peptide (divalent peptide3A5) against TLR4/MD-2 | Syngeneic mouse models | Treatment improved efficacy of anti-PD-1 Ab with reduced lung metastasis |