Anti-CD3D monoclonal antibody, clone C-C22 [FITC]

Polymorphism of the genes encoding the alpha, beta, and gamma chains of the human T-cell receptor (TCRA, TCRB, and TCRG), insulin gene (INS), and three closely linked polymorphic genes on chromosome 11q23, Thy-1 (THY1), T3-D (CD3D), and c-ets proto oncogene (ETSl) were investigated among 56 unrelated patients with insulin-dependent diabetes mellitus (IDDM) and 48 healthy controls. Only eight of the 17 enzymes examined revealed restriction fragment length polymorphism (RFLP), with the use of TCRA, TCRB, and TCRG. No significant association was observed. Polymorphism after BglI, SstI, and TaqI digestion was observed for the INS gene. In consideration of the three classes within the insulin-gene-linked DNA polymorphism alleles, Al and more rarely A2 alleles were found, but with no significant frequencies. THYl and CD3D genes were polymorphic after MspI digestion but no significant association was observed. Conversely, the ETSl gene showed polymorphism after TaqI, SstI, and AvaII were used. Only a significant AvaII-polymorphic fragment (p < 0.03) was found. However, this significant association disappeared when the corrected p value was applied. These results were compared to findings in Caucasians and some differences were noted. The polymorphism observed in this study may be useful in genetic studies on immunologically affected populations.

Background: Preclinical studies show that TLR9 agonists can eradicate leukemia by induction of immune responses in vivo against AML and ALL. These studies demonstrated that TLR9 agonists induce an immediate NK response followed by adaptive T and B cells responses resulting in long term anti-leukemia immunity. Methods: The Therapeutic Advances in Childhood Leukemia and Lymphoma Phase I consortium performed a pilot study on 3 patients with MRD positive acute leukemia after an initial remission on conventional chemotherapy (TACL T2009-008) with the TLR 9 agonist (GNKG168). To guide future trial development, we evaluated the impact of GNKG168 by Nanostring on the expression 608 genes before and 8 days after initiation of GNKG168 therapy. Results: Twenty-three out of 578 markers on the nanostring panel showed significant difference (p <= 0.05). We focused on 8 markers that had the greatest differences with p < 0.01. Two genes were increased, promyelocytic leukemia protein (PML) and H-RAS, and 6 were decreased, Single Ig and TIR Domain containing (SIGIRR, IL1R8), interleukin 1 receptor 1 (IL1RL1, ST2), C-C Motif chemokine receptor 8 (CCR8), interleukin 7 R (IL7R), cluster of differentiation 8B (CD8B), and cluster of differentiation 3 (CD3D). Tumor inhibitory pathways were downregulated including the SIGIRR (IL1R8), important in IL-37 signaling and NK cell inhibition. TLR9 can induce IL-33, which is known to downregulate ST2 (IL1RL1) a receptor for IL-33. Conclusion: GNKG168 therapy is associated with immunologic changes in pediatric leukemia patients. Further work with a larger sample size is required to assess the impact of these changes on disease treatment and persistence of leukemia remission.