For decades, cancer vaccines have promised much and delivered little. Early “off-the-shelf” approaches struggled to generate durable immune responses or meaningful clinical benefit, particularly in solid tumors.
But according to Alessandro Riva, CEO of Transgene, that narrative is changing.
In a recent interview, Riva explained how Transgene is building a new generation of individualized cancer immunotherapies, combining personalized neoantigen vaccines with engineered viral platforms to unlock stronger, longer-lasting anti-tumor immune responses.
Two Complementary Platforms, One Goal: Activating the Immune System Against Cancer
Transgene’s strategy is built around two distinct but complementary platforms, each designed to stimulate the immune system differently.
1. Individualized Neoantigen Therapeutic Vaccines (myvac® platform)
The first platform is a highly personalized therapeutic cancer vaccine.
Here’s how it works:
- Each patient’s tumor is genetically analyzed
- Patient-specific mutations (neoantigens) are identified
- These neoantigens are encoded into a viral vector
- The resulting vaccine is administered to the patient
The objective is clear:
Induce a targeted immune response against mutations unique to that patient’s tumor
Unlike preventive vaccines, this is a therapeutic vaccine, designed not to prevent cancer, but to treat and potentially cure it.
2. Oncolytic Virus Platform: Direct Tumor Killing + Immune Activation
Transgene’s second platform is based on engineered oncolytic viruses.
These viruses are designed to:
- Selectively infect and replicate inside tumor cells
- Destroy cancer cells from within
- Release immune-stimulating payloads embedded in the virus
The dual effect is powerful:
- Direct tumor cell killing
- Amplified immune activation occurs as tumor antigens are released
Although the technologies are very different, both platforms share the same end goal:
stimulating a robust and durable immune response against cancer.
Why Earlier Cancer Vaccines Failed, and Why This Time Is Different
Riva is clear-eyed about the history of cancer vaccines.
Traditional off-the-shelf therapeutic vaccines, built around shared tumor antigens, largely failed to demonstrate meaningful survival benefits. The problem wasn’t vaccination itself; it was the lack of personalization.
The new generation of vaccines changes that.
“This new chapter is based on individualized mutations, not shared mutations.”
By targeting neoantigens unique to each patient, these vaccines are far more likely to trigger a stronger and more precise response.
This approach appears particularly promising in early-stage solid tumors, where the immune system is more intact and more capable of being activated.
Clinical Proof of Concept: No Relapses in Vaccinated Patients
At the American Society of Clinical Oncology (ASCO), Transgene presented data that marks an important milestone for personalized cancer vaccines.
In a randomized Phase 1 study in early-stage head and neck cancer:
- Patients receiving Transgene’s personalized vaccine experienced zero relapses
- Median follow-up exceeded 30 months
- All patients were followed for at least two years
- In the control arm, three relapses were already observed among 16 patients
This result is particularly striking given the biology of head and neck cancer, a tumor type considered immunologically “cold”, where immune cells typically struggle to infiltrate the tumor.
“This is an important proof of principle for us.”
Deep and Durable Immune Responses Confirmed
Beyond clinical outcomes, Transgene also demonstrated strong immunological validation.
At the Society for Immunotherapy of Cancer (SITC), the company showed that:
- Over 70% of patients developed a de novo immune response against the selected neoantigens
- These immune responses persisted for more than two years
- The responding T cells showed memory phenotypes, suggesting long-term immune surveillance
Together, these findings confirm not only efficacy signals but also durable immune engagement, a key requirement for long-term cancer control.
What’s Next: Expanding into a Randomized Phase 2 Study
Building on the Phase 1 results, Transgene is now advancing into a randomized Phase 2 study.
Key next steps include:
- Completing Phase 2 enrollment (expected in 2026)
- Expanding the dataset to approximately 70–72 patients
- Addressing tumor heterogeneity in a larger population
- Confirming clinical and immunological signals at scale
The combined Phase 1 and Phase 2 population will form a robust proof-of-concept dataset for Transgene’s personalized vaccine approach.
A New Era for Therapeutic Cancer Vaccines?
According to Alessandro Riva, the implications extend beyond a single program.
The convergence of:
- Advanced tumor sequencing
- Personalized neoantigen selection
- Viral delivery platforms
- Immune monitoring technologies
may finally unlock the long-sought promise of therapeutic cancer vaccines.
Not to prevent cancer, but to treat it, control it, and potentially cure it.
If the Phase 2 results confirm early findings, Transgene’s approach could mark a pivotal shift in how solid tumors are treated in the years ahead.
Here it is in video format if you prefer to watch:
