tumor-infiltrating

ADH-503 (GB1275) is a potent agonist of the integrin CD11b to mitigate myeloid cell immunosuppression.

AZ10397767 is a potent CXCR2 antagonist (IC50 = 1 nM). AZ10397767 significantly reduced the numbers of infiltrating neutrophils into both in vitro and in vivo tumor models.

Mitazalimab (ADC-1013; JNJ-64457107) is an FcγR-dependent CD40 agonist that exhibits directed activity against tumors. By activating antigen-presenting cells, such as dendritic cells (DC), it triggers the initiation of tumor-reactive T cells. Consequently, Mitazalimab promotes the infiltration and destruction of tumors by tumor-specific T cells and remodels the tumor-infiltrating myeloid microenvironment [1] [2].

F5446 is a SUV39H1 inhibitor. F5446 has an EC50 of 0.496 μmol/L for SUV39H1 enzymatic activity. H3K9me3 was enriched in the promoters of GZMB, PRF1, FASLG, and IFNG in quiescent T cells. F5446 inhibited H3K9me3, thereby upregulating expression of these effectors in tumor-infiltrating CTLs and suppressing colon carcinoma growth in a CD8+ CTL-dependent manner in vivo. Our data indicate that SUV39H1 represses CTL effector gene expression and, in doing so, confers colon cancer immune escape.

(Z)-Leukadherin-1 (ADH-503 free base) is an allosteric agonist of CD11b.

CB-1158-analog, also known as Numidargistat-analog and INCB01158-analog, is a potent and orally active arginase inhibitor with IC50=89 nM) . CB-1158 blocked myeloid cell-mediated suppression of T cell proliferation in vitro and reduced tumor growth in multiple mouse models of cancer, as a single agent and in combination with checkpoint blockade, adoptive T cell therapy, adoptive NK cell therapy, and the chemotherapy agent gemcitabine. CB-1158 increased tumor-infiltrating CD8+ T cells and NK cells, inflammatory cytokines, and expression of interferon-inducible genes. CB-1158 may be potentially useful in renal cell cancer, breast cancer, non-small cell lung cancer, acute myeloid leukemia, and other tumor types where arginase-secreting MDSCs are known to play an immunosuppressive role. (see ADDITIONAL INFORMATION in this web page for CB-1158 structure confusion).

Tyrosinase (206-214), human (AFLPWHRLF), is a 9-amino acid peptide and an epitope of tyrosinase that can be recognized by HLA-A24 restricted, tumor-infiltrating lymphocytes (TIL) [1].

PD-L1-IN-2, a Naamidine J derivative, serves as a promising antineoplastic immunomodulator by hindering PD-L1 activity. In vivo studies indicate that it suppresses PD-L1 expression and amplifies tumor-infiltrating T-cell response, thus exerting anticancer effects. This compound is particularly utilized in the investigation of colorectal cancer [1].

SWS1, a d-(+)-biotin-conjugated PD-L1 inhibitor (IC50: 1.8 nM), displays anticancer activity by augmenting tumor-infiltrating lymphocytes and demonstrating anti-tumor efficacy, as evidenced by a 66.1% tumor growth inhibition (TGI=66.1%) in the B16-F10 mouse model [1].