Reinduction Of Cancer/testis Antigens And In Vivo Generation Of Antigen Specific Cytotoxic Lymphocytes Enhance Adoptive Immunotherapy In Mouse Lymphoma Model

Background:Nowadays, much progress has been made in the treatment of hematological malignancies. However, a significant number of patients develop disease recurrence even after hematopoietic stem cell transplantation (HSCT). It is urgent to develop novel strategies to promote remission and prolong the survival of these patient populations by using alone or in combination with standard therapy. Cancer/testis antigens (CTAs) are ideal candidates for cancer immunotherapy because of their restricted expression profile in normal tissues. However, so far the outcome of immunotherapy targeting CTAs has been rather disappointed in clinical setting because CTAs are down-regulated by CpG methylation in their promoter regions. Methods:We re-induced mouse CTA P1A by treatment of demethylation agent 5-aza-2-deoxycytidine (5-aza-dCyd) and generated P1A-specific cytotoxic lymphocytes (CTLs) by immunizing BALB/C mouse with dendritic cell pulsed with P1A-specific peptide, established a tumor-bearing animal model in BALB/C mouse, observed the killing activities of P1A-specific CTL in vitro and in vivo. Results:We found that the demethylation of P1A promoter facilitated the proper homing of P1A-specific CTLs and its recognition of the target cells. Moreover, P1A specific CTLs had specific cytotoxic effect against target cells both in vitro and in vivo. Finally, we showed that similar to CD8+CTLs, CD4+T lymphocytes played a crucial role in eradicating tumor cells. Conclusion:Taken together, our results suggest that the induced CTA is a potential target for adoptive immunotherapy of cancer.