blinatumomab作用机制(文献1)
在研药物
Solitomab/AMG110/MT110 (EpCAM + CD3)
AMG111, MT111, MEDI565(CEA + CD3)
Pasotuxizumab, AMG112, MT112(PSMA + CD3)
AMG330(CD33 + CD3)
AMG420, BI836909(BCMA + CD3)
DART(dual-affinity retargeting)
DART是MacroGenics的技术平台。DART比BiTE具有更好的结构和生物学特性,包括更好的稳定性和T细胞对恶性细胞的细胞毒性作用的最佳重定向。
文献2
PF06671008 P-cadherin + CD3
Flotetuzumab, MGD006 CD123 + CD3
MGD007 gpA33 + CD3
MGD009 B7H3 + CD3
MGD010 CD32B + CD79B
MGD011, JNJ64052781 CD19 + CD3
Ozoralizumab, ATN103 TNF + HSA (Ablynx)
ALX0061 IL6R + HSA(Ablynx, AbbVie)
ALX0761 L17A/F + HSA(Ablynx, Merck)
ALX0141 RANKL + HSA(Ablynx)
参考文献
Sergey E Sedykh et al,Bispecific antibodies: design, therapy, perspectives,Drug Des Devel Ther . 2018 Jan 22;12:195-208.
Ling Huang et al, Multispecific, Multivalent Antibody-Based Molecules Engineered on the DART® and TRIDENT TM Platforms,Curr Protoc Immunol . 2020 Jun;129(1):e95.
Joanie Del Bano et al,Taking up Cancer Immunotherapy Challenges:Bispecific Antibodies, the Path Forward? Antibodies (Basel),. 2015 Dec 26;5(1):1.
Gleason MK, Verneris MR, Todhunter DA, Zhang B, McCullar V, Zhou SX. Bispecific and trispecific killer cell engagers directly activate human NK cells through CD16 signaling and induce cytotoxicity and cytokine production. Mol Cancer Ther 2012;11:2647–84.
Vallera DA, Felices M, McElmurry R, McCullar V, Zhou X, Schmohl JU, et al. IL15 trispecific killer engagers (TriKE) make natural killer cells specific to CD33+ targets while also inducing persistence, in vivo expansion, and enhanced function. Clin Cancer Res 2016;22:3440–50.
Maria-Elisabeth Goebeler et al,T cell-engaging therapies - BiTEs and beyond,Nat Rev Clin Oncol . 2020 Jul;17(7):418-434
Daniel A.Vallera et al,IL15 Trispecific Killer Engagers (TriKE) Make Natural Killer Cells Specific to CD33þ Targets While Also Inducing Persistence, In Vivo Expansion, and Enhanced Function,Clin Cancer Res; 22(14) July 15, 2016