Identification of Novel Survivin-Derived CTL Epitopes with Different HLA-A-Restriction Profiles

Abstract

The identification of tumor antigens, which are essential for the survival of tumor cells is a new avenue to prevent antigen loss variants emerging due to immunoselection, particularly during immune therapy. In the search for such immunogenic tumor antigens, we recently identified spontaneous cytotoxic lymphocyte (CTL) responses against the inhibitor of apoptosis protein survivin. Thus, we identified two HLA-A2-restricted, survivin-derived CTL epitopes, which both were targets for spontaneous CTL responses in melanoma, breast cancer, and CLL. Here, we extend these data and describe the characterization of novel HLA-A1-, HLA-A2-, HLA-A3-, and HLA-A11-restricted survivin epitopes on the basis of spontaneous CTL responses in cancer patients. These epitopes significantly increase the number of patients eligible for immunotherapy based on survivin derived peptides. Additionally, the collective targeting of several restriction elements is likely to decrease the risk of immune escape by HLA-allele loss.

Association of survivin splice variants with prognosis and treatment of breast cancer

“…This will lead to more specific survivin vaccines that would elicit better immune response, generate immune memory and offer protection from tumor progression [44] . The development of antibodies is still costing a large amount of money and there are several considerations for their use [19,45] .…”

“…Survivin is a tumor-associated antigen so it could be a potential target for immunotherapy [34] . During the search for immunogenic tumor antigens, spontaneous CTL responses against survivin were identified [45] . Survivin is an attractive target for vaccination since immune escape by down regulation or loss of expression of this protein would impair sustained tumor growth.…”

Identification and characterization of survivin‐derived H‐2Kb‐restricted CTL epitopes

“…The availability of multiple survivin epitopes presented by different HLA restriction elements further reduces the risk of immune escape and thereby might improve therapeutic effectiveness. While several survivin-derived CTL epitopes are known in humans [19,20,31,32], there are only limited reports for the murine system [27,33].…”

“…The availability of multiple survivin epitopes presented by different HLA restriction elements further reduces the risk of immune escape and thereby might improve therapeutic effectiveness. While several survivin-derived CTL epitopes are known in humans [19,20,31,32], there are only limited reports for the murine system [27,33].In the present study, we identified two H-2K were carried out as described [36]. The assembly assay is based on stabilization of the class I molecule after loading of peptide to the peptide transporter-deficient cell line RMA-S.…”

Immunotherapy in allogeneic hematopoietic stem cell transplantation – not just a case for effector cells

“…47 Another 'shared' antigens is survivin, a member of the inhibitor of apoptosis protein family. 48,49 Survivin is an inhibitor of the effector caspases 3 and 7 resulting in blockade of the mutual downstream events of both the death-receptormediated and mitochondrial apoptosis pathways. 50 Association with early events in leukemogenesis is documented in patients with myelodysplastic syndrome (MDS) by an increase in survivin expression prior to development of overt leukemia.…”