As Elicio Therapeutics awaits a phase 2 readout of its lymph node-targeting therapeutic cancer vaccine in humans, the biotech has published fresh preclinical data showing the same tech boosted the efficacy of T cell receptor-modified T-cell (TCR-T) therapy in mice.
In a paper published Jan. 25 in the journal Cancer Immunology Research, Elicio scientists described experiments in which they paired the company’s amphiphile (AMP) platform—which “vaccinates” lymph nodes with adjunct therapies that boost the TCR T-cell response—with TCR T-cells in three different mouse models of cancer. The treatment enhanced the cells’ proliferation and ability to destroy cancer cells, in some cases completely destroying the animals’ tumors, according to the paper.
“Tumor growth in mice treated with AMP vaccination in concert with TCR T-cell infusion was significantly delayed or completely eradicated compared with therapy with TCR T-cells alone or in combination with [a control] vaccination,” the scientists wrote in their paper. “Consequently, AMP-vaccinated mice had significantly enhanced long-term survival without signs of distress.”
The researchers injected adult female mice with one of three different types of tumor cells that had already developed resistance to TCR T-cell monotherapy. They then injected the mice with one of three vaccines: an AMP vaccine, which directs the adjuvants it carries to the lymph nodes; a form of the vaccine that does not accumulate in the lymph nodes; or a control solution.
This was followed by TCR T-cells aimed at the appropriate target antigen for the cancer model. The antigens were NY-ESO-1, HPV E7 and mutated KRAS, all of which are associated with tough-to-treat solid tumor types such as esophageal cancer, cervical cancer and pancreatic cancer.
"The lymph nodes are critical for orchestrating the mechanisms which define tumor-directed immune responses," Pete DeMuth, Ph.D., chief scientific officer at Elicio, told Fierce Biotech Research in an email. "Here, we wanted to ask whether delivery to lymph nodes was important for allowing vaccines to (1) coordinate the expansion and functional qualities of tumor-specific TCR-T cells and (2) more broadly promote immune activation, which could contribute to improved anti-tumor effect."
The AMP vaccines appeared to deliver on both fronts. Around 30% of the mice that received the AMP vaccine with TCR T-cells survived beyond day 80 of the study; all the mice that received a non-AMP version of the vaccine died by day 60, and all those that received a control solution died by around day 30.
To see if the treatment could prevent relapse, mice that survived beyond day 80 were dosed again with tumor cells. The TCR T cells persisted in all of the mice in the follow-up cohort and prevented the growth of secondary tumors, the researchers reported.
Besides providing more validation for Elicio's strategy in a few different cancer types, the results are a positive signal for Elicio’s KRAS-targeting therapeutic cancer vaccine, dubbed ELI-002. Data published in early January from a phase 1 clinical study of the original formulation of the vaccine showed that 84% of patients, who had either pancreatic or colorectal cancer that is resistant to immunotherapy, had biomarker responses indicating T-cell activation and tumor response. It also delayed relapse and reduced the risk of death in the patients.
"If phase 2 data is positive, we will work with the FDA and health authorities around the world to provide any additional data required for approval," he added.