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Copyright ©The Author(s) 2016.
World J Gastroenterol. Jul 28, 2016; 22(28): 6362-6372
Published online Jul 28, 2016. doi: 10.3748/wjg.v22.i28.6362
Table 1 Gene mutations in human colorectal cancer
PathwaysCell cycleWNTMAPKTGFP53PI3K-AktApoptosis
GenesMLH1[71]APC[71]KRAS[72]SMAD4[73]P53[74]PTEN[75]DCC[76]
MSH2[71]CTNNB1[77]PLA2G2A[78]NRAS[79]BAX[80]
MSH6[81]MCC[82]PTPN12[83]PIK3CA[84]
RAD54B[85]AXIN2[86]FGFR3[87]
CCND1[88]ARID1AAKT1[89]
BUB1B[90]SOX9
AURKA[91]
EP300[92]
Table 2 Completed clinical trials of immunotherapy in human colorectal cancer
Ref.Clinical phaseNo. patientsClinical settingImmunotherapyComments
Morse et al[93]II74Liver or lung metastases from CRC removed by surgeryPANVAC-V + PANVAC-F + DC/PANVAC-V + PANVAC-F + GM-CSFGood safety record
Vermorken et al[44]II and III254Colon cancerActive specific immunotherapy (ASI) with an autologous tumor cell- bacillus Calmette-Guérin (BCG) vaccine with surgical resection/resection aloneASI gave significant clinical benefit in surgically resected patients in stage II colon cancer
Dukes' stage B2-C380Colon or rectal cancerASI with an autologous tumor cell-BCG vaccineASI may be beneficial to patients with colon cancer
Hanna et al[94]Stage II and Stage IIIColon cancerASI consisting of autologous tumor cells mixed with BCG (OncoVAX™)Increase 5-yr survival rate and 5-yr disease-free survival rate, reduce recurrence rate
Marshall et al[95]Stage IVColon cancerALVAC-CEASafe and can elicit CEA-specific CTL responses
Harris et al[96]Stage II and stage III412Colon cancerAdjuvant active specific immunotherapy with an autologous tumor cell-BCG vaccineMore beneficial than resection alone
Table 3 Ongoing immunotherapy clinical trials in human colorectal cancer
TypeCancerPhaseNameIdentifierStart time
Monoclonal antibodiesUntreated metastatic colorectal cancerIIRO5520985 (a bispecific anti-ANG-2/anti-VEGF-ANCT021412955/15/2014
Colorectal cancerI/IIIMMU-132 (an Ab-drug conjugate targeting Τrop-2)NCT016315526/26/2012
Metastatic colorectal cancerI/IIIMMU-130 (an Ab-drug conjugate targeting CEACAM5)NCT016053185/22/2012
Metastatic colorectal carcinomaIMGD007 (a dual-affinity re-targeting DART protein designed to target the glycoprotein A33)NCT022488059/18/2014
Metastatic colorectal cancerIOMP-131R10 (an anti-RSPO3 Ab)NCT024824416/19/2015
Immune checkpoint inhibitorsMSI positive/negative colorectal cancerIIMK-3475 (an Ab that blocks negative signals on T cells)NCT018765116/10/2013
MSI positive colorectal cancerIIpilimumabNCT0206018812/18/2013
MSI negative colorectal cancerIINivolumabNCT0206018812/18/2013
Colorectal cancerIMED14736NCT0197583110/29/2013
Colon cancerI/IIAnti-CD27 (Varlilumab) and NivolumabNCT0233591812/18/2014
Cancer vaccinesMetastatic colorectal cancerIIDC vaccineNCT0261557411/24/2015
Colorectal cancerIAVX701 (targets CEA)NCT018902136/26/2013
Metastatic colorectal carcinomaISGI-110 in combination with an allogeneic colon cancer cell vaccine (GVAX) and cyclophosphamide (CY)NCT0196628910/10/2013
Colorectal cancerIHER-2 vaccineNCT013765056/9/2011
Adoptive cell therapyMetastatic colorectal cancerIITIL (tumor-infiltrating lymphocytes)NCT011741217/31/2010
Colorectal cancerI/IIAnti-MAGE-A3-DP4 TCRNCT021118504/9/2014
Colorectal carcinomaI/IICAR T cellsNCT0261713411/26/2015
Colorectal cancerINK cells + CliniMACs CD3 and CD56 systemsNCT007207857/22/2008
Oncolytic virus therapiesKRAS mutant metastatic Colorectal cancerIREOLYSIN in combination with FOLFIRI and BevacizumabNCT012746241/7/2011
Adjuvant immunotherapiesRecurrent colorectal cancerI/IIChemokine modulatory regimenNCT015451412/29/2012
CytokinesColorectal carcinomaIAM0010 (a recombinant human IL-10)NCT0200944912/2/2013
Colorectal carcinomaIRh IL-15NCT015724934/5/2012