Anti-TTK monoclonal antibody Made to order

Kalimeris indica (L.) Sch. Bip. is a traditional Chinese medicine (TCM) and a portion of food used for cooking in China. It has been demonstrated that an ethanol extract of K. indica has an anti-inflammatory effect by inhibition of nitric oxide (NO) production on murine macrophage RAW264.7 cells after lipopolysaccharide (LPS) induction. In this study, the hepatoprotective effects of the total phenolics of K. indica (TPK), the total triterpenes of K. indica (TTK), and the total flavones of K. indica (TFK) from ethanol extracts of K. indica were evaluated in Bacille Calmette-Guerin (BCG)/LPS-induced liver injury in vivo. The treatments of TPK, TTK, and TFK improved liver injury in mice. Additionally, all treatments significantly not only reduced the hepatic malondialdehyde (MDA) content and hepatic total nitric oxide synthase (tNOS) but also induced the hepatic superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity. The treatments of TPK and TTK significantly reduced the hepatic inducible nitric oxide synthase (iNOS). The treatments of TPK, TTK, and TFK reduced the serum total bilirubin (T-Bil), and only TFK treatment reduced the serum alanine aminotransferase (ALT). Our results suggest that TPK, TTK, and TFK from ethanol extracts of K. indica might play an essential protective role against BCG/LPS-induced liver injury in vivo.

MHC-bound peptides from aberrant proteins may be a specific immunotherapeutic target on cancer cells. Because of difficulties in identifying such antigens, viral or model antigens have so far been used to study their biological relevance. We here identify a naturally existing human T-cell epitope derived from a truncated protein. The antigenic peptide is derived from the gene TTK only through an alternative transcript containing a premature termination codon that may target the transcript for nonsense-mediated decay (NMD). This antigen is recognized by HLA-A(+) 02:01-restricted CD8 thorn T cells derived from an allotransplanted leukemia patient. Functional analyses showed that these T cells failed to recognize several HLA-matched primary leukemic cells that expressed the alternative TTK transcript. Conventional antigen processing and presentation were not affected, suggesting that leukemic cells modify the generation of antigens processed from aberrant proteins. This natural TTK epitope provides insights in the source of transcripts producing antigenic epitopes in healthy and leukemic cells. Our data underscore potential pitfalls of targeting NMD-derived or other unconventionally generated epitopes as immunotherapeutic approach.