In their quest to proliferate and spread, cancer cells will do anything they can to avoid being killed. Most often they develop mechanisms to suppress attacks by their would-be killers — immune cells. One way researchers and clinicians fight back against this suppression is with cancer vaccines that help immune cells recognize and attack cancer cells.
But recognizing tumor cells is just one half of the equation. Often, immune cells surrounding the tumor create an immune-suppressive environment themselves, making it even harder for cancer drugs to work. The team at the cancer vaccine company IO Biotech, however, came up with a solution.
“Not only are we targeting the cancer cells, we're also targeting the immune-suppressive cells with our technology, and that seems to really mediate a much better response in terms of eradications of the tumor cells themselves,” said Mai-Britt Zocca, the Founder and Chief Executive Officer of IO Biotech.
As the Chief Executive Officer at IO Biotech, Mai-Britt Zocca leads the company’s cancer vaccine research.
Credit: IO Biotech
By targeting both tumors and the misbehaving immune cells in the tumor microenvironment (TME), the researchers at IO Biotech created an off-the-shelf cancer vaccine that has so far shown promise in treating metastatic melanoma as well as other solid tumors.
“If we hit the data that we anticipate in Phase 3, the sky is the limit. It really has potential in any cancer indication,” Zocca said.
In new data presented at the recent American Association for Cancer Research meeting (AACR 2025), they revealed new mechanistic insight into how their melanoma vaccine works as well as preclinical results for their new vaccine that targets transforming growth factor beta (TGF-β).
The IO Biotech team noticed that while many solid tumors overexpress indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death ligand (PD-L) 1, suppressive immune cells including regulatory T cells and tumor-associated macrophages in the TME did too. So, they decided to develop a peptide-based cancer vaccine called IO102-IO103 that could target the two antigens in both the tumor and the surrounding immune cells.
“What we have seen with the peptides is that we are generating a strong and lasting T cell response, which is what you really are looking for,” said Zocca.
They found that when they paired the vaccine with the immune checkpoint inhibitor nivolumab in a Phase 1/2 trial of people with advanced or metastatic melanoma, it worked surprisingly well.
“We really had very encouraging data that has not been seen ever before, even in a smaller study,” said Qasim Iftikhar Ahmad, IO Biotech’s Chief Medical Officer. In addition to a strong safety readout, patients had very high response rates — the median progression-free survival was 26 months (1). With these encouraging results, the IO Biotech team began a Phase 3 clinical trial comparing IO102-IO103 plus the anti-PD-1 immunotherapy pembrolizumab versus pembrolizumab alone. They fully recruited participants to the trial by December 2023, and they plan to readout the primary endpoint of progression-free survival in Q3 of this year.
We really had very encouraging data that has not been seen ever before, even in a smaller study.
- Qasim Iftikhar Ahmad, IO Biotech
In a poster presentation at AACR 2025, the researchers showed that each component of the dual cancer vaccine promoted specific gene expression changes in the tumor; the PD-L1 component led to improved cytotoxic T cell activity, and the IDO1 antigen reduced the immune suppression in the TME (2).
Because cancer treatments can have high toxicities or result in severe side effects, the IO Biotech team was encouraged to see that their dual-peptide cancer vaccine has so far proven very safe.
“We've had at least five safety reviews by the independent committee, and the safety profile seems quite clean, with no added systemic toxicity on top of what you would expect from pembrolizumab alone,” said Ahmad. “It also opens our gates for further exploration in other indications, even other combinations, mainly as we see safety as a clear benefit here.”
Because IDO1 and PD-L1 are upregulated in other solid tumors, the IO Biotech team is also running a Phase 2 basket study testing IO102-IO103 plus pembrolizumab in metastatic non-small cell lung cancer, squamous cell carcinoma of head or neck, and metastatic urothelial bladder cancer.
Qasim Iftikhar Ahmad is the Chief Medical Officer at IO Biotech.
Credit: IO Biotech
The researchers also released new preclinical data at the meeting on their cancer vaccine that targets TGFβ, a pathway implicated in many types of cancers. Inhibiting TGFβ systemically has not had clinical success, but based on prior research that found that healthy donor T cells killed cancer cells expressing TGFβ, the team developed a vaccine that specifically targeted TGFβ-specific T cell epitopes (3). Working in mouse models of pancreatic and prostate cancer, the researchers found that the vaccine led to the expansion and activation of TGFβ-specific T cells ex vivo. They also saw a reduction in tumor volume in the animals.
“What is particularly interesting for TGFβ is that it's a target where, basically, you have been trying to drug that target for 30 years or more,” said Zocca. “If our method works out, it will really be a very safe way of targeting also TGFβ.”
Most of all, Zocca and Ahmad are proud to see the positive response rates their therapies have had in patients so far.
“Combination therapies come with a lot of toxicity, and it becomes difficult to get efficacy. You don't really get the full benefit for the patient in real life because of the toxicity,” said Ahmad. “What we could offer here is an opportunity for those patients to get the full benefit of the treatment, which then, as Mai-Britt was saying, results in the outcome in totality: efficacy, safety, and quality of life. That would be amazing.”
References
- Kjeldsen, J.W. et al. A phase 1/2 trial of an immune-modulatory vaccine against IDO/PD-L1 in combination with nivolumab in metastatic melanoma. Nat Med 27, 2212-2223 (2021).
- Chapellier, M. et al. Abstract 2241: Immune-modulatory therapeutic cancer vaccines against IDO1 and PD-L1 control tumor growth through target specific changes in the tumor microenvironment. Cancer Res 85, 2241 (2025).
- Joseph, J.V. et al. Abstract 2257: A TGFβ-directed immune-modulatory vaccine induces T cell activation and drives antitumor activity by modulating the tumor microenvironment. Cancer Res 85, 2257 (2025).
