Expanding cancer immunotherapy by exploiting recall immunity – a new co-therapy option for checkpoint inhibitor

Immune checkpoint inhibitors (CIs) have emerged as a revolutionary treatment for several cancer types. They enhance immune recognition by silencing checkpoints and allowing T-cells to attack tumor cells. Despite the significant improvement in prognosis for some cancer patients, there are challenges in using CIs for the treatment of all cancers.

To address this challenge, SRI International has developed a novel immunotherapy that is capable of delivering previously encountered antigenic peptides specifically to cancer cells and facilitating their presentation through the MHC class I pathway. This new therapy utilizes a synthetic nanoparticle delivery system comprising three components: a neutral stealth liposome, encapsulated synthetic immunogenic HLA class I restricted peptides derived from the measles virus (MV), and a tumor-targeting peptide on the external surface of the liposome.

The targeting peptide results in accumulation of the liposomes specifically inside cancer cells, and facilitates presentation of the MV-derived immunogenic peptides specifically in HLA class I molecules. SRI International refers to this system as, “Targeted Antigen Loaded Liposomes” (TALL). Therefore, TALL can generate a strong secondary immune response specifically against the targeted tumor cells in a patient who has been previously vaccinated against, or infected by, MV.

In short, the strategy is attempting to trick the immune system into responding as though the cancer cell is infected with MV without the use of a viral particle. SRI International has shown that treatment with TALL alone substantially reduces the growth of lung, triple-negative breast, and pancreatic tumors in mice.

In this Xtalks webinar, SRI Biosciences researcher Indu Venugopal discusses how TALL can successfully be used in combination with existing immunotherapies, like checkpoint inhibitors, to generate a robust cytotoxic T lymphocyte response directed specifically against the tumor, resulting in a drastic reduction of tumor burden.