Updates on NeoVax, a Vaccine for CLL

At the 2025 Intercepting Blood Cancers (IBC) conference held in Nice, France, Marwan Kwok, MD, PhD, of Dana-Farber Cancer Institute, presented results from a phase 1 clinical trial of the CLL vaccine NeoVax during a session titled “Updates on vaccination as an early intervention strategy in CLL.”

To understand how NeoVax works, refer to our original article here: A Personalized CLL Vaccine Being Studied for Patients in Watch and Wait: NeoVax 

Below, we provide the latest updates from the study. 

NeoVax Phase 1 Updates for CLL

CLL and the Immune System

Patients with CLL often have compromised immune systems. Given that cancer vaccines depend on the immune system’s ability to recognize and attack cancer cells, the question arises: Can a cancer vaccine be effective in CLL?

The clinical trial’s phase 1 focused on CLL patients with unmutated IGHV who were not yet eligible for standard treatments.

Initially, researchers assessed whether CLL patients had enough targets for a successful personalized vaccine. The study found that 7 out of 9 patients had adequate targets to proceed with vaccination. Four of these patients have completed their therapy, while three are still in treatment.

Does NeoVax Recruit CLL-Killing Immune Cells? 

The team then investigated whether NeoVax could trigger an immune response strong enough to fight CLL cells.

Despite patients’ compromised immune systems, researchers discovered that NeoVax could indeed mobilize immune cells, specifically CD4+ and CD8+ T-cells, to target CLL. This was confirmed through various testing methods which showed that these T-cells were actively killing CLL.

Can NeoVax Stop CLL Progression? 

The study also looked at whether early treatment with NeoVax could alter the cancer’s progression. Initially, NeoVax by itself appeared effective in reducing cancer cells. However, about 10 months post-vaccination, the cancer often advanced, requiring patients to start treatment with venetoclax and obinutuzumab, standard CLL therapies.

In the group where a patient received NeoVax with low-dose cyclophosphamide, the additional treatment significantly enhanced the vaccine's effectiveness, leading to a sustained reduction in cancer cells. The trial investigators also plan to introduce pembrolizumab to counteract T-cell exhaustion and support the long-term effectiveness of the vaccine.

Key Takeaways

NeoVax successfully recruits cancer-fighting T-cells, initially reducing CLL cell counts. However, when NeoVax is given by itself, the effect is temporary, as cancer cell counts tend to rise again about 10 months after vaccination due to T-cell exhaustion. 

Investigators are now exploring different combinations to enhance the vaccine’s effectiveness for a longer period of time. 

Are there any more updates on CLL therapies?