Study On The Anti-tumor Effect Of WT1 Peptide Vaccine In Vitro And In Mice

WT1 protein is over expressed not only in various types of leukemia but also in more than 80% solid tumor. All the facts including the consistency of high expressed WT1 with cell malignancy conversion or malignancy cells'mass proliferation, the inverse correlation between WT1 expression levels and prognosis of leukemia, the inhibition of WT1 expression by WT1-antisense oligomers inducing tumor cells growth stopping, show that the WT1 is essential for cancer cell's malignancy proliferation. It is impossible that tumor cells loss or downregulat its expressing of WT1 protein to escape immunotherapy targeting WT1 protein. These results suggest that the WT1 peptides promise targets for immunotherapy against malignant tumor.There is no investigation report about immunotherapy against malignant tumor with WT1 peptides internal for the moment, whereas it has been studied in vitro, in mice in vivo and clinical trials overseas, and has gotten a certain curative effect, but the efficiency of clinical trials is only 60%, and no any effect, even tumor is still progressing in some patients. So many problems still need to be solved before peptide vaccine of WT1 can be used to cure or prevent malignant tumor.It is can be found out through analyzing all the abroad studies that there is a crossing phenomena in specific CTLs killing target cells, i.e., a certain WT1 peptide specific CTLs can kill certain tumor cells, but can't lysis the other tumor cells, whereas another WT1 peptide specific CTLs can kill the later, but can't lyse the former. It can be suspected that even tumor cell over express WT1 protein, and the antigen determent of these WT1 protein can be presented in the tumor surface by the same HLA-I molecules as the WT1 peptide specific CTLs. But the HLA-I molecules can conjugate a certain kind of peptide which have a compatible anchor motifs, other than a fixed WT1 peptide, so WT1 peptide specific CTLs can't always recognize and conjugate enough correspond AD to kill tumor cells. Muli-WT1 peptide vaccine can not only raise the rate of specific-CTLs catching the AD in tumor cell surface, but also can avert the tumor escaping from immune surveillance due to the dominant AD modulation in repeating application of WT1 peptide vaccine. Theoretically, if one peptide vaccine's efficiency rate in the crowd is 60%, two peptide vaccine's efficiency rate in crowd will reach 84%〔60%+(100%-60%)×60%〕, three will be 93.6%〔84%+(100%-84%)×60%〕. So, combined- application of Muli-WT1 peptide vaccine can improve efficiency in the crowd, theoretically.Before being recognized by precursor of specific CTLs and activate specific CTLs, small peptide vaccine AD must bind with the HLA-I molecules on the APC surface. Scince Muli-WT1...