Embryonic Stem Cell Vaccine Versus Hepatic Stem Cell Vaccine In Prophylaxis And Treatment Of Subcutaneous Implantable Hepatoma In Mouse

Background&Objective: It was found that cancer cells share several oncofetalantigens or other cell surface molecules with both embryonic stem cells (ESCs) andadult stem cells (ASCs). Thus the application of ESC or ASC as a prophylaxis andtherapeutic cancer vaccine was expected to generate immune responses against theseshared antigens or molecules, thereby eliminating the cancer cells or even cancer stemcells (CSCs). The aim of this study was to determine and compare the effectiveness ofESC and ASC vaccine in prophylaxis and treatment of subcutaneous implantable hepatoma in mouse.Methods:1.10-14week-old C57BL/6mice were divided into5groups, with10micein each group. The ESC vaccination group one and hepatic stem cell (HSC) vaccinationgroup one received ESC vaccine and hepatic oval cell (HOC) vaccine three times at anone-week interval respectively, followed by subcutaneous inoculation of live hepatomacell line one week later; whereas the control group received subcutaneous inoculation oflive hepatoma cell line without vaccination. To investigate the long-term prophylacticbenefits of ESC and HOC vaccination, ESC vaccination group two and HSCvaccination group two received ESC and HOC vaccine three times at an one-weekinterval respectively, followed by subcutaneous inoculation of live hepatoma cell linefour weeks later.2. Age, sex and initial tumor burden-matched mice were divided into3groups, with5mice in each group. The ESC treatment group and HSC treatment groupreceived ESC and HOC treatment weekly for three weeks, respectively. However micebearing hepatoma in the control group received no treatment. Tumor formation rate,growth rate, and tumor volume were monitored and compared between groups. Theendpoint for this study was one tumor diameter≥15mm or earlier if tumor ulcerated, atwhich point mice were euthanized and tumors were weighed.Results:1. Tumor formation rate of mice was1/10in ESC vaccination group one and0/10in HSC vaccination group one respectively, both were significantly lower than thatin the control group (P<0.05). Moreover the average growth rate of subcutaneoushepatoma was significantly reduced in both ESC vaccination group one and HSCvaccination group one, in comparison with the control group (P<0.05). When we furtherinvestigated the long-term (4weeks) prophylactic benefits of ESC and HSC vaccination,we found that the reduced tumor formation rate of mice and decreased tumor growthrate of subcutaneous hepatoma were modest in the ESC vaccination group two (P>0.05),but significant in the HSC vaccination group two (P<0.05) compared with the controlgroup. Tumors were weighed at day31post tumor inoculation when all mice weresacrified. The average weight of tumors were0.0000gram (g) in HSC vaccinationgroup one,0.0005g in HSC vaccination group two,0.0071g in ESC vaccination groupone,0.0413g in ESC vaccination group two,0.1122g in control group, respectively.2.When we further investigated the role of ESC vaccine and HSC vaccine in treatment ofsubcutaneous implantable hepatoma, we found that the tumor growth rate of mice wassignificantly reduced in both ESC treatment group and HSC treatment group versus the control group (P<0.05). Furthermore,2/5mice with implantable hepatoma achieved“stable disease”(which is characterized as neither a50%decrease in tumor burden nora25%increase compared with baseline) following ESC treatment,4/5mice withimplantable hepatoma achieved “complete response”(which is characterized as thedisappearance of all lesions) after HSC treatment, whereas all the mice in control groupsuffered “progressive disease”(which is characterized as more than25%increase intumor burden compared with the baseline). At day31when mice were sacrified, theaverage weight of tumors were0.0190g in HSC treatment group,0.0577g in ESCtreatment group, and0.2085g in control group, respectively.Conclusions:1.Both ESC vaccination and HSC vaccination are effective in prophylaxisof subcutaneous implantable hepatoma in one week.2. The benefit of ESC vaccinationin prophylaxis of subcutaneous implantable hepatoma is diminished in four weeks,whereas HSC vaccination is still effective in prophylaxis of subcutaneous implantablehepatoma in four weeks.3. Both ESC vaccine and HSC vaccine are effective intreatment of subcutaneous implantable hepatoma, but the therapeutic effect of HSCvaccine is superior to ESC vaccine.