Neoepitope yeast vaccine(Nantbioscience, Inc.)

Cancer is characterized by genetic instability due to accumulation of somatic mutations in the genes which generate neoepitopes (mutated epitopes) for targeting by Cytotoxic T lymphocytes (CTL). Breast cancer has a high transformation rate with unique composition of mutational burden and neoepitopes load that open a platform to designing a neoepitopes-based vaccine. Neoepitopes-based therapeutic cancer vaccines designed by neoantigens have shown to be feasible, nontoxic, and immunogenic in cancer patients. Stimulation of CTL by neoepitope-based vaccine of self-antigenic proteins plays a key role in distinguishing cancer cells from normal cells and selectively targets only malignant cells. A neoepitopes-based vaccine to combat breast cancer was designed by combining immunology and bioinformatics approaches. The vaccine construct was assembled by the fusion of CTL neoepitopes, helper sequences (used for better separation of the epitopes), and adjuvant together with linkers. The neoepitopes were identified from somatic mutations in the MUC16, TP53, RYR2, F5, DNAH17, ASPM, and ABCA13 self-antigenic proteins. The vaccine construct was undertaken to study the immune simulations (IS), physiochemical characteristics (PP), molecular docking (MD) and simulations, and cloning in appropriate vector. Together, these parameters establish safety, stability, and a strong binding affinity against class I MHC molecules capable of inducing a complete immune response against breast cancer cells.Communicated by Ramaswamy H. Sarma.

The development of vaccines, especially RNA-based, directed against patient-specific tumor neoepitopes is an active and productive area of cancer immunotherapy. Promising clinical results in melanoma and other solid tumor types are emerging. As with all cancer therapy modalities, neoepitope vaccine development and delivery also has some drawbacks, including the level of effort to develop a patient-specific product, accuracy of algorithms to predict neoepitopes, and with the exception of melanoma and some other tumor types, biopsies of metastatic lesions of solid tumors are often not available. We hypothesize that in some circumstances the use of rationally designed combinations of “off-the-shelf” agents may prove an additional path to enable the patient to produce his/her own “neoepitope vaccine” in situ. These combination therapies may consist of agents to activate a tumor-associated T-cell response, potentiate that response, reduce or eliminate immunosuppressive entities in the tumor microenvironment, and/or alter the phenotype of tumor cells to render them more susceptible to immune-mediated lysis. Examples are provided in both preclinical and clinical studies in which combinations of “off-the-shelf” agents lead to the generation of T cells directed against tumor-derived neoepitopes with consequent antitumor activity.