Background TALL^TM is a nanomedicine-based cellular immunotherapy for delivering synthetic antigenic peptides specifically to cancer cells and facilitating their presentation through the MHC Class I pathway, generating a robust secondary immune response against tumor cells. TALL^TM comprises of three components: a liposome shell, encapsulated synthetic immunogenic HLA class I restricted peptides derived from measles virus, and a tumor-targeting peptide (called MGS5) on the liposome surface, which binds to a novel tumor-specific biomarker. In addition to evaluating its potential as a standalone immunotherapy, we have also determined the efficacy of combining TALL^TM with an immune checkpoint inhibitor (ICI).

Methods In vitro and in vivo studies to demonstrate the high tumor-specificity of MGS5 and TALL^TM liposomes were performed using flow cytometry, confocal microscopy and IVIS imaging. In vitro experiments were conducted to characterize the MOA of TALL^TM, including biomarker/receptor identification for MGS5. Immunoprofiling studies along with staining of tumor tissues were used to confirm the increase in memory CD8⁺T-cells in tumors. Studies were conducted in C57BL/6 and Balb/c mice bearing syngeneic pancreatic (Pan02) and triple-negative breast (4T1) cancers respectively to demonstrate the efficacy of both TALL alone as well the TALL and anti-PD1 ICI combination immunotherapy.

Results Treatment with TALL^TM substantially reduced tumor growth in both cancer models. TALL and ICI combination treatment showed complete response in breast cancer models and resulted in a 10-fold reduction in tumor burden in pancreatic cancer models, while completely halting metastasis. Analysis of tumor tissues showed a 10-fold increase in the presence of CD8⁺T-cells in TALL-treated animals. Our receptor identification studies determined that MGS5 binds to a novel cancer biomarker: N-glycolylneuraminic acid (Neu5Gc)-Sialyl Lewis^A.

Conclusions TALL^TM is an excellent immunotherapy which can be synergistically used with ICIs, due to its ability to convert immune-cold tumors to immune-hot, by generating a robust cytotoxic T lymphocyte response directed specifically against the tumor.