Cancer and Immunotherapy · us
Viral Immunotherapy for Prostate Cancer: Local Immune Activation Still Seen Two Years After Treatment
Candel’s new analysis links a lower risk of recurrence with immune signals in tumor tissue and blood, offering biological clues for combining viral therapy with radiation therapy; however, the small blood study and exploratory findings are not yet sufficient to demonstrate systemic protection against cancer.
For cancer that remains confined to the prostate, the challenge of treatment is not only to eliminate the existing tumor, but also to keep the disease from returning for years. Candel Therapeutics announced an integrated analysis on September 30 showing that, following treatment with the investigational viral immunotherapy aglatimagene besadenovec (CAN-2409) combined with radiation therapy, signs of immune activation were still visible in local tissue two years later, and T-cell changes were also observed in the blood. These findings offer clues to more durable disease control, but do not yet establish that the immune changes caused the clinical benefit.
CAN-2409 uses a replication-deficient adenovirus to deliver the herpes simplex virus thymidine kinase gene into tumors. In combination with oral valacyclovir, it causes some cells to die and release tumor antigens, thereby triggering immune recognition. The phase 3 PrTK03 trial used a randomized, double-blind design to compare viral therapy with placebo; both groups received valacyclovir and external beam radiation therapy, with optional androgen deprivation therapy.
OncLive and Urology Times reported that this update focused on 635 intermediate-risk patients. After a median follow-up of 58 months, the relative risk of prostate cancer recurrence or death from prostate cancer was 41% lower in the viral therapy group than in the control group, with a hazard ratio of 0.59 and a 95% confidence interval of 0.41 to 0.84. This was an analysis of prostate cancer-specific disease-free survival in the intermediate-risk subgroup and cannot be directly interpreted as an improvement in overall survival. It also differs from the primary endpoint for the full trial, which counted recurrence or death from any cause.
Biopsies provided another layer of evidence. Among 277 intermediate-risk patients with evaluable biopsy samples, the proportion with no tumor detected 22 to 26 months after treatment was 76.6% in the viral therapy group and 60.7% in the control group. An exploratory digital pathology analysis also found a higher proportion of lymphocytes within residual tumors in the viral therapy group. The increase in immune cells in biopsy samples supports the possibility of sustained changes in the local environment; however, the absence of cancer cells in a single biopsy does not mean the disease has been permanently eliminated.
The changes in blood came from the ongoing phase 2a PrTK05 study. According to Urology Times, this open-label trial plans to enroll 45 people, while the immune analysis released so far covers only 13 patients who received viral therapy combined with radiation therapy and 6 patients who received radiation therapy. The treatment group showed expansion of circulating CD8-positive T-cell populations, including cells bearing proliferation and cytotoxicity markers. The company said that formal comparisons with the control group were still ongoing, so these findings cannot yet establish a systemic immune effect.
Other clinical results also require careful interpretation. Analyses of time to biochemical recurrence, metastasis, and initiation of salvage anticancer treatment were all exploratory and descriptive. Although the hazard ratios favored viral therapy, the confidence intervals were relatively wide, and those for biochemical recurrence and salvage treatment included 1, meaning that no difference between the groups could not be ruled out. These signals can help frame questions for subsequent research, but are not yet sufficient to confirm efficacy for each outcome.
Candel plans to submit a biologics license application to the U.S. Food and Drug Administration in the fourth quarter of 2026, including biodistribution and viral shedding data from PrTK05; CAN-2409 is currently not approved for use. The significance of this integrated analysis lies in providing tissue- and blood-level clues that may help explain the long-term clinical results. Whether these immune signals can predict efficacy in individual patients, and the treatment’s full benefits and risks, still require clarification through more comprehensive analyses and regulatory review.