2304 - Synthetic peptide of tumor–associated antigen L6 formulated with polymer-based adjuvant enhances anti-tumor effects in mice

Background

Tumour associated antigen L6 (TAL6) is a cell surface protein of the transmembrane-4 superfamily (TM4SF) also known as TM4SF1. TAL6 is over-expressed in more than 80 % of human lung, breast, colon and ovarian tumours but not normal tissues. Synthetic peptides are attractive for cancer immunotherapy because of their safety and flexibility. We have identified an B cell epitope of TAL6 using monoclonal antibodies. The synthetic peptide epitope formulated with adjuvants can induce anti-tumour immunity.

Methods

The linear B cell epitope was identified by anti-TAL6 monoclonal antibody using overlapping peptides cover the extracellular domain of TAL6. The synthetic peptide containing B cell epitope was formulated with different adjuvants to immunize mice to determine their immunogenecity. Furthermore, the sera of immunized mice were used to examine the antibody-dependent cellular cytotoxicity (ADCC) against human cancer. Moreover, the anti-tumor effects were evaluated in mouse model.

Results

The anti-TAL6 recognized a minimal linear region at amino acid 121-129. We formulated synthetic peptide (a.a.114-133) and a pan-DR peptide with different adjuvants to immunize mouse and evaluate their immunogenicity. The peptides formulated with an emulsion type nanoparticle (PELC) adjuvant and a toll-like receptor 9 agonist (CpG ODN) (PELC/CpG) induced the greatest ADCC responses in TAL6-expresssed cell lines. The induced anti-tumor immunity inhibited the growth of TAL6-positive cancer cells in mouse.

Conclusions

These data suggested that a peptide containing B cell epitopes of TAL6 formulated with PELC/CpG adjuvant is feasible for cancer immunotherapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Ministry of Science Technology, Taiwan.

Disclosure

All authors have declared no conflicts of interest.