Copyright ©The Author(s) 2016.
World J Gastroenterol. Sep 7, 2016; 22(33): 7440-7452
Published online Sep 7, 2016. doi: 10.3748/wjg.v22.i33.7440
Table 1 Rationales of each combination therapy
Checkpoint inhibitor plus cytotoxic agentsEnhance cellular immunityEfficacy may be influenced by timing when cytotoxic agents add
Augment dendritic cell maturationSevere myelosupression may interrupt immune checkpoint therapy
Reduce MDSC and Tregs
Decreases CAF
Combination with checkpoint inhibitorsActivate tumor immunity by different mannarir AE will increase
Provide synergy efficacy even in immune resistant tumor
Checkpoint inhibitor plus T cells stimulate agentsActivate tumor immunity by different mannarSevere AE including cytokine storm may occur
Deactive Tregs
Checkpoint inhibitor plus cancer vaccineIncrease the presentation of taas
Enhance PD-L1 expression
RadiotherapyEnhance cross priming of ctlsOptimal schedule and dose are not established
Enhanse abscopal effect
Table 2 Problems of each combination therapy
TreatmentDiseasePhaseClinical trial numberStatus
Checkpoint inhibitor plus cytotoxic agents
Ipilimumab (anti-CDLA-4)PC1NCT01473940Ongoing
Nivolumab (anti-PD-1)PC1NCT02309177Ongoing
Nab-PTX ± gemcitabine
Combination with checkpoint inhibitors
Nivolumab (anti-PD-1)TNBC, GC, PC,1, 2NCT01928394Ongoing
Ipilimumab (anti-CTLA-4)SLCL. BC, OC
MEDI4736 (anti-PD-1)Solid tumor1NCT02261220Ongoing
Tremelimumab (anti-CTLA-4)
Nivolumab (anti-PD-1)Cervical cancer, BC, CRC, HN, GC, HCC, melanoma, NSCLC1, 2NCT01968109Ongoing
BMS-986016 (anti-LAG-3)
PDR001 (anti-PD-1)Solid tumors1, 2NCT02608268Ongoing
MBG453 (anti-TIM-3)
Ipilimumab (anti-CDLA-4)B7-H3 expressing tumors (melanoma, HN, NSCLC)1, 2NCT02381314Ongoing
MGA271 (anti-B7-H3)
Pembrolizumab (anti-PD-1)B7-H3 expressing tumors1, 2NCT02475213Ongoing
MGA271 (anti-B7-H3)(melanoma, HN, NSCLC)
Checkpoint inhibitor plus T cells stimulate agents
Nivolumab (anti-PD-1)Solid tumors, B-cell NHL1, 2NCT02253992Ongoing
Urelumab (anti-4-1 BB)
Pembrolizumab (anti-PD-1)Solid tumors1NCT02179918Ongoing
Urelumab (anti-4-1 BB)
Tremelimumab (anti-CTLA-4)Solid tumors1, 2NCT02205333Ongoing
MEDI6469 (anti-OX-40
MEDI4736 (anti-PD-L1)Solid tumors1, 2NCT02205333Ongoing
MEDI6469 (anti-OX-40)
Tremelimumab (anti-CTLA-4)Melanoma1NCT01103635Ongoing
CP-870,893 (anti-CD40)
Checkpoint inhibitor plus cancer vaccine
Ipilimumab (anti-CTLA-4) + GVAXPC2Ref 58Terminated
FOLFIRINOX followed byPC2NCT01896869Ongoing
Ipilimumab (anti-CTLA-4) + GVAX
Nivolumeb (anti-PD-1) + GVAXPC2NCT02243371Ongoing
Checkpoint inhibitor plus raditaion
Ipilimumab + radiationMelanoma1NCT01557114Terminated