Just like snowflakes we are all unique (at least genetically speaking), and unfortunately for modern medicine so are our cancers. This individuality in cancers, even of the same type or subtype, means that there is no single cure-all. However, researchers, like those at the from Washington University in St. Louis and The University of Oklahoma, are now delving into the complexity of these diseases in order to find a way to use their uniqueness against them.
In melanoma there exists patient-specific neoantigens – antigens associated with tumor cells. These antigens are T-cell derived and usually directed against tumor-encoded amino acid substitutions (AAS), in other words tumor missense mutations.
The authors, led by Gerald Linette from Washington University in St. Louis, postulated that these tumor missense mutations may be perceived by the body as foreign antigens, creating a suitable avenue for patient-specific immunotherapy where the AAS-derived neoantigens will elicit tumor-specific T-cell immunity.
To test their hypothesis, they performed genomic analysis of AAS peptides on surgically excised tumors from three patients with stage III resected cutaneous melanoma. From each of the patients the team selected seven AAS peptide candidates, which were incorporated into a personalized vaccine containing melanoma gp100-derived peptides. Peripheral blood mononuclear cells (PMBC) were collected from the patients prior to vaccination and weekly post-vaccination.
The researchers then went on to perform immunologic analysis of these collected PMBCs and found:
- Pre-vaccine immunity to three neoantigens existed in all patients.
- Patient-specific vaccination increased T-cell response to neoantigens, with observed frequencies of 23%, 64%, and 89% across the three patients respectively.
- Additionally, the vaccination elicits T-cell immunity to two other neoantigens with variable observable frequencies across individual patients.
- Moreover, the vaccination also activated a pool of naïve and unschooled tumor-specific T cells.
Encouragingly, all the three patients are alive and are without any adverse immune reactions.
Get to know your enemies over in Science, April 2015.