Turning Cold Tumours Hot: TCR Evidence Behind TREOS Bio's Cancer Vaccine

Can a peptide cancer vaccine make a cold tumour fight back, and then keep fighting? In episode 7 of Repertoire Room, Sander Wuyts speaks with Eniko Toke, Chief Scientific Officer and co-founder of TREOS Bio, about the TCR sequencing evidence behind PolyPEPI1018, an off-the-shelf peptide vaccine developed for metastatic microsatellite-stable (MSS) colorectal cancer, a tumour type that responds poorly to checkpoint inhibitors alone because so few T cells infiltrate it.

Designing a vaccine around shared tumour antigens

PolyPEPI1018 targets seven shared tumour antigens through twelve immunogenic peptide fragments. Rather than selecting these fragments from a single patient's biopsy, TREOS Bio built an in silico human model representing around 85% of global HLA diversity, validated against the immune response rates of previous cancer vaccine trials. That model identified the fragments most likely to trigger a broad immune response across a diverse patient population, the basis for an off-the-shelf, rather than personalised, product.

Confirming vaccine-induced T cells reach the tumour

In the OBERTO-301 Phase 2 trial, run in collaboration with Mayo Clinic, TREOS Bio combined PolyPEPI1018 with the checkpoint inhibitor atezolizumab in patients with late-stage, refractory MSS metastatic colorectal cancer. Paired biopsies taken before and during treatment showed increased T cell infiltration and rising PD-L1 expression, evidence the tumour was reacting to an expanding T cell pool. To confirm those T cells were the ones the vaccine was designed to generate, TREOS Bio worked with ImmuneWatch: DETECT was trained on PolyPEPI1018-specific TCR sequences isolated from donor blood, then used to match those sequences against T cells identified in the tumour biopsies. The workflow confirmed that vaccine-induced T cells expanded in both blood and tumour, a level of TCR-specific confirmation Eniko describes as "not possible a few years ago."

Antigen spreading: a vaccine effect beyond its own design

The TCR data also captured antigen spreading: T cells targeting tumour antigens never included in the vaccine, including mutant KRAS, appeared after treatment, while bystander T cells specific to pathogens stayed unchanged. That pattern points to the cancer immunity cycle reactivating more broadly than the vaccine alone targets, and it lines up with a further finding: broader, more diverse tumour-reactive T cell responses correlated with longer progression-free survival, a pattern TREOS Bio has now observed across three separate trials.

About the guest

Eniko Toke is Chief Scientific Officer and co-founder of TREOS Bio, where she leads the science behind the company's HLA-guided peptide vaccine platform, drawing on a career spanning immunology, computational biology, and pharmaceutical drug development. TREOS Bio's next step is a larger, randomised Phase 2 study in MSS colorectal cancer, alongside continued development of a companion diagnostic to identify likely responders.

Listen to the full episode: YouTube | Spotify