Tumor antigens as targets for cancer immunotherapy

Nathalie Vigneron

The success of cancer immunotherapy lies on the activation of anti-tumor cytolytic T lymphocytes, which are able to recognize and kill tumor cells. Identifying the optimal antigens to induce anti-tumor responses is therefore important to increase the specificity and efficacy of therapies such as cancer vaccine or adoptive T cell transfer. Over the years, in collaboration with the Van den Eynde lab, we have identified a number of antigenic peptides recognized by CTLs on tumors. These include peptides derived from tumor antigens such as gp100 (Michaux et al., 2014; Vigneron et al., 2004), MAGE-A1 (Stroobant et al., 2012) or MAGE-C2 (Ma et al., 2004; Ma et al., 2011). In collaboration with Dr Edus Warren at the Fred Huchinston Institute in Seattle, we also identified several antigens, which are derived from small nuclear polymorphisms, and are recognized by CTLs isolated from recipients of allogeneic hematopoietic stem cell transplants from major histocompatibility complex-matched donors (Tykodi et al., 2008; Warren et al., 2006).

With the aim of guiding scientists and clinicians searching for the most appropriate cancer vaccine candidates, we and several other PI’s at the de Duve institute started compiling what we think are the most relevant human tumor antigens. The cancer peptide database (CAPED) was therefore created and is available on https://caped.icp.ucl.ac.be. This database is regularly updated by searching the literature for new antigenic peptides.

List of publications

Ma, W., C. Germeau, N. Vigneron, A.S. Maernoudt, S. Morel, T. Boon, P.G. Coulie, and B.J. Van den Eynde. 2004. Two new tumor-specific antigenic peptides encoded by gene MAGE-C2 and presented to cytolytic T lymphocytes by HLA-A2. Int J Cancer 109:698-702.

Ma, W., N. Vigneron, J. Chapiro, V. Stroobant, C. Germeau, T. Boon, P.G. Coulie, and B.J. Van den Eynde. 2011. A MAGE-C2 antigenic peptide processed by the immunoproteasome is recognized by cytolytic T cells isolated from a melanoma patient after successful immunotherapy. Int J Cancer 129:2427-2434.

Michaux, A., P. Larrieu, V. Stroobant, J.F. Fonteneau, F. Jotereau, B.J. Van den Eynde, A. Moreau-Aubry, and N. Vigneron. 2014. A spliced antigenic peptide comprising a single spliced amino acid is produced in the proteasome by reverse splicing of a longer peptide fragment followed by trimming. J Immunol 192:1962-1971.

Stroobant, V., N. Demotte, R.M. Luiten, R.M. Leonhardt, P. Cresswell, A. Bonehill, A. Michaux, W. Ma, A. Mulder, B.J. Van den Eynde, P. van der Bruggen, and N. Vigneron. 2012. Inefficient exogenous loading of a tapasin-dependent peptide onto HLA-B*44:02 can be improved by acid treatment or fixation of target cells. Eur J Immunol 42:1417-1428.

Tykodi, S.S., N. Fujii, N. Vigneron, S.M. Lu, J.K. Mito, M.X. Miranda, J. Chou, L.N. Voong, J.A. Thompson, B.M. Sandmaier, P. Cresswell, B. Van den Eynde, S.R. Riddell, and E.H. Warren. 2008. C19orf48 encodes a minor histocompatibility antigen recognized by CD8+ cytotoxic T cells from renal cell carcinoma patients. Clin Cancer Res 14:5260-5269.

Vigneron, N., V. Stroobant, J. Chapiro, A. Ooms, G. Degiovanni, S. Morel, P. van der Bruggen, T. Boon, and B.J. Van den Eynde. 2004. An antigenic peptide produced by peptide splicing in the proteasome. Science 304:587-590.

Warren, E.H., N.J. Vigneron, M.A. Gavin, P.G. Coulie, V. Stroobant, A. Dalet, S.S. Tykodi, S.M. Xuereb, J.K. Mito, S.R. Riddell, and B.J. Van den Eynde. 2006. An antigen produced by splicing of noncontiguous peptides in the reverse order. Science 313:1444-1447.