Naturally occurring immune response against biologically and clinically relevant targets

Background

Few studies evaluate the immunogenicity of biological relevant targets in tumors with high-world prevalence and early relapse such as ovarian, triple negative breast cancer (TNBC), multiple myeloma (MM), etc. Some tumor targets are immunogenic but are not relevant for tumor survival such as CEA, CA-125, CA-19-9, etc. and have failed in vaccines clinical trials. Only a few studies focus on the biological and clinical relevance of tumor antigens such as MUC1, Her-2, etc. Aberrant up-regulation of some proteins that are involved in cancer relapse has shown to be a mechanism by which some auto-proteins become immunogenic and potentially targets of both humoral and cellular adaptive immune response. We evaluated whether putative relevant proteins that are found in high incidence of several cancers and associated with poor prognosis could be recognized by the humoral immune response. We further interrogate if the humoral immune response against these proteins may predict relapse and overall survival.

Methods

Four broad-spectrum proteins known to be overexpressed in several tumors and associated with early relapse were identified by systematic reviews. Indirect peptide ELISA was used to evaluate humoral immune response using all predicted peptides from these proteins. 50 stage IV cancer patients and 50 age-matched controls were studied. We identified those MHC-I and MHC-II peptides using computer-based algorithms from Ape-1, Fascin, RCAS1 and VCP.

Results

Fascin and VCP peptide mixes are immunogenic in all cancer-interrogated patients and in some controls. Antibody responses were significantly elevated in cancer patient's sera when compared to controls (Ape-1 p = ns, Fascin p = 0.0016, RCAS1 p = ns and VCP p  0.38 against at least 2 peptides for 2 proteins had better overall survival (p = 0.005).

Conclusions

Discussion: All tumors studied reacted by peptide indirect ELISA at least against 2 peptides of overexpressed proteins involved in important biologic pathways and this is the first approach to design a broad spectrum multi-peptide vaccine to prevent relapse. Humoral immune response may also predict the clinical outcomes in malignancies that tend to relapse in short period of time.

Clinical trial identification

DOES NOT APPLY

Legal entity responsible for the study

Centro de Investigación de Cáncer en Sonora

Funding

Centro de Investigación de Cáncer en Sonora

Disclosure

All authors have declared no conflicts of interest.