ImMucin™: A novel therapeutic vaccine with promiscuous MHC binding for the treatment of MUC1expressing tumors


Antitumor vaccination using tumor-associated antigens (TAAs) is considered a safe and specific methodology for controlling metastases in cancer patients [1–3]. The rationale behind this approach is that cancer cells that express TAAs in association with their MHC molecules can be subject to recognition and destruction by tumor-specific T cells. However, since these vaccines are often derived from less immunogenic selfTAAs and are used to treat Abbreviations: CTL, cytotoxic T lymphocytes; DC, dendritic cells; mAb, monoclonal antibody; SI, stimulation index; SP, signal peptide; TAA, tumor-associated antigen; TRA, tandem repeat array; VCs, vaccine candidates. Corresponding author at: Vaxil BioTherapeutics Ltd., 3 Hana Robina St., Tel Aviv 69372, Israel. Tel.: +972 8 9396948; fax: +972 8 9396996. Email address: (L. Carmon). 1 R.K. and I.V. contributed equally to this work. sick individuals, frequently with compromised immune systems, they should be able to induce a strong and preferably a broad immune response [4].
One approach used to improve a specific immune response was to construct a multiepitope vaccine that makes use of a mixture of specific MHC class I epitopes derived from different TAAs [5,6]. However, even the enhanced cytotoxic T lymphocytes (CTL) antigenic repertoire in such vaccines could not compensate for the lack of panHLA response [7], since they usually comprised of a single MHC class I-restricted epitope. Moreover, these vaccines also lacked MHC class II restricted T helper epitopes. In a few cases, the lack of MHC class II epitopes in such vaccines was shown to induce immunological tolerance to the immunizing antigens [8], rather than long lasting immunity mediated via CD8+ T cell activation. In the past, the limited number of known TAAderived MHC class II epitopes has led to the use of nonspecific ‘universal’ MHC class IIrestricted epitopes [9]. In one report, the use of a panHLA class II epitope peptide (PADRE) increased the response against the helper epitope, but the elevation in CD8+ T cell effectors specific to the MHC class I-restricted epitope was limited [10]. Click here to download the full research article