Point receptorsCompound (Synonym) BMS (Nulojix) CTLA4 fusion-Ig, costimulation blocker FDA approval
intravenous, FDA Agency for Food and Drug Administraton, EMA European Medicines Agency, ADCC PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28914615 antibody Ira K, Imai H, Shimizu K, Nakano T, Shames DS et dependent cellular cytotoxicity, NHL non-Hodgkin lymphoma, PTCL peripheral T-cell lymphoma, TAA tumor related antigenPage 7 ofGreil et al. Targeting of TSA would in theory get rid of the bystande.Point receptorsCompound (Synonym) BMS (Nulojix) CTLA4 fusion-Ig, costimulation blocker FDA approval 15.11.2011 EMA approval 07.07.2011 Compound (Trade name) Drug type (application) Status Indication Prophylaxis of renal graft rejection Prophylaxis of renal graft rejection Rhematoid arthritis; Polyarticular juvenile idiopathic arthritis Untreated follicular lymphoma Relapsed/refractory M. Hodgkin Myelodysplastic syndromes Acute myeloid leukemia Cutaneous T-NHL, PTCLDrug Target (Synonym)Effect on T-cells and immune systemCD80 (B7-1) CD86 (B7-2)T-cell costimulation blocker, inhibits T-cell Belatacept proliferation and production of cytokines (LEA29Y)Abatacept Galiximab (IDEC-114) Decitabine Romidepsin (FR901228) MedImmune Fusion protein Recombinant CD137-L protein Gloucester Pharmaceuticals, Depsipeptide, (i.v. Q1W) Celgene (Istodax) Janssen-Cilag (Dacogen) Biogen Humanized MAb IgG1, (i.v.) Phase I/II Phase IIBMS (Orencia)CTLA4 fusion-Ig, costimulation blockerFDA approval 31.07.2011 EMA approval 25.01.Greil et al. Cell Communication and Signaling (2017) 15:CDActivates ADCC on B-NHL cells with upregulated CDCD80 DNMTUpregulation of CD80 on cancer cells - > costimulatory activation of T-cellsDeoxycytidine analogue, FDA approval 02.05.2006 i.v. (D1-5, Q6W) EMA approval 28.09.2012 FDA approval 05.11.2009 EMA refused approval 09.07.2012 Preclinical Phase ICD86 HDACUpregulation of CD86 on cancer cells, HDAC-I - > costimulatory PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26080418 activation of T-cellsCD137-LInduction of differentiation of AML cell samples in vitroIn vitro Advanced solid tumorsCD252 (OX40-L)Binds and activates Ox40 by mimicking MEDI-6383 Ox40-L - > proliferation of TAA distinct T-effector cells - > activation of anti-tumor immune response Oxelumab (huMAb OX40L) (R4930) Enoblituzumab (MGA-271) MGD-009 MacroGenics MacroGenics GenentechCD252 (OX40-L)Binds and inhibits Ox40L plus the interaction with Ox40 - > inhibition of allergen induced immune responseHuman MAb IgG1, (i.v.)Phase IIMild allergic asthmaCD276 (B7H3)Inhibits CDHumanized MAb IgG1, (i.v.) Dual affinity retargeting proteinPhase I Phase IB7-H3 expressing refractory strong tumors B7-H3 expressing unresectable or metastatic strong tumorsCD276 (B7H3) CDRedirection of T-cells to kill B7-H3 overexpressing tumor cellsMAb indicates monoclonal antibody, i.v. intravenous, FDA Agency for Meals and Drug Administraton, EMA European Medicines Agency, ADCC PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28914615 antibody dependent cellular cytotoxicity, NHL non-Hodgkin lymphoma, PTCL peripheral T-cell lymphoma, TAA tumor connected antigenPage 7 ofGreil et al. Cell Communication and Signaling (2017) 15:Page eight ofhigh costs, novel and far better predictors of response are as a result necessary. Notably, the mutational burden defined because the variety of mutations per megabase, may well correlate with -and thus predict the occurrence of- tumor-specific (neo)antigens (TSA) which are expressed on the tumor cell surface and presented to T-cells. T-cells exposed to TSA can learn to especially target and remove (ie kill) tumor cells. In contrast to tumor-associated antigens (TAA), which are in essence massively overexpressed `normal antigens' that also take place on standard, non-cancerous tissues of the body, TSA are accurate neoantigens that can not be identified on any non-malignant cell.