Aglatimagene Boosts Immune Infiltration in Localized Prostate Cancer

Adding aglatimagene besadenovec (CAN-2409) to external beam radiation therapy (EBRT) was associated with greater lymphocyte infiltration of prostate tissue and greater lymphocyte-residual tumor interaction in patients with localized, intermediate- to high-risk prostate cancer, according to a digital pathology analysis presented at the 2026 American Society for Radiation Oncology (ASTRO) Annual Meeting.^1,2

The analysis drew on prostate biopsies from the phase 3 PrTK03 trial (NCT01436968). Among 427 evaluable posttreatment biopsies, intratumoral lymphocyte fraction across all tissue regions was higher in the aglatimagene arm (n= 282 biopsies) than in the placebo arm (n = 145 biopsies; P = .048). In a paired analysis of 108 patients whose posttreatment biopsies contained residual tumor (aglatimagene, n = 62; placebo, n = 46), the change from baseline favored aglatimagene for intratumoral lymphocyte fraction (P = .006), lymphocyte/tumor enrichment score (P = .003), and lymphocyte-tumor mixing score (P < .001).^1,2

"While radiation therapy alone drives immune infiltration into prostate tumors, these data support that aglatimagene produced a qualitatively distinct immune response," Francesca Barone, MD, PhD, chief scientific officer of Candel Therapeutics, and presenting author of the poster, stated in a news release.² "The significantly greater lymphocyte infiltration and sustained lymphocyte-tumor engagement which we observed, more than [2] years after treatment, supports durable immune remodeling rather than transient inflammation."

Clinical and Pathologic Outcomes in PrTK03

Aglatimagene is a replication-defective adenoviral vector that carries the herpes simplex virus thymidine kinase (HSV-tk) gene. The PrTK03 trial randomly assigned 745 patients with newly diagnosed disease 2:1 to intraprostatic aglatimagene or placebo, each given with oral valacyclovir and radiotherapy with or without short-course androgen deprivation therapy.

In previously reported findings, the trial met its primary end point of disease-free survival (DFS), defined as time to cancer recurrence or death from any cause.³ At a median follow-up of 50.3 months, the risk of a DFS event was 30% lower with aglatimagene (HR, 0.70; 95% CI, 0.52-0.94; P = .0155), according to results published in The Lancet Oncology. A prostate-specific antigen nadir below 0.2 ng/mL was reached by 67.1% of patients in the aglatimagene arm vs 58.6% in the placebo arm (P = .0164).

After central review by at least 2 blinded independent readers, 167 of 209 evaluable patients (80%) in the aglatimagene arm had a negative biopsy vs 62 of 98 (63%) in the placebo arm (P = .0018) at 22 to 26 months after EBRT.

Digital Biopsy Analysis

Hematoxylin and eosin slides from biopsies taken before and after study treatment were digitized for the analysis.^1,2 The samples came from 647 patients who received all 3 planned injections. Machine learning models, trained on pre- and postradiation datasets that expert pathologists had annotated, classified individual cells as tumor cells or lymphocytes and classified tissue as neoplastic, stromal, or other. The 2 outputs were then overlaid to quantify cell types within each tissue compartment. In all, 622 pretreatment and 427 posttreatment biopsies could be evaluated.

The paired analysis included only patients whose posttreatment slides showed tumor on pathologist review. Within tumor regions of interest, the investigators calculated 3 spatial measures that were all found to be increased with aglatimagene. Intratumoral lymphocyte fraction captures how abundant lymphocytes are inside tumor regions. The lymphocyte enrichment score captures whether lymphocytes sit closer to tumor cells than a random distribution would predict. The lymphocyte-tumor mixing score captures how much lymphocytes and tumor cells intermingle, as opposed to tumor cells clustering with one another.

Differences between arms in the change from baseline were tested with analysis of covariance. The investigators noted that the P-values for these measures are nominal and were not adjusted for multiple comparisons.

Immune Findings in Residual Tumor

Radiation therapy was itself linked to immune infiltration. Lymphocyte fraction across all tissue regions was higher in the 427 posttreatment samples than in the 622 pretreatment samples (P < .001), and the investigators reported that the rise occurred in both arms.

Among the 108 patients with residual tumor, mean enrichment scores were similar in the 2 arms at baseline and then diverged, rising with aglatimagene and falling with placebo. Intratumoral lymphocyte fraction and mixing score rose in both arms, with larger gains in the aglatimagene arm.

The investigators concluded that finding this pattern in biopsies that remained positive for tumor supports the hypothesis that ongoing immune surveillance contributes to local tumor control with aglatimagene. Barone stated that the mechanism may help explain the DFS and pathologic outcomes that were observed.

Aglatimagene currently holds FDA fast track and regenerative medicine advanced therapy designations for newly diagnosed localized prostate cancer in patients with intermediate- to high-risk disease, and Candel stated its intention to submit a biologics license application.²

REFERENCES

1. Barone F, Dwyer J, Manzanera A, et al. Digital pathology in relation to immune activation following aglatimagene besadenovec immunotherapy in localized prostate cancer. Presented at: 2026 American Society for Radiation Oncology Annual Meeting; September 26-30, 2026; Boston, MA. Abstract LBA 30.

2. Candel Therapeutics Announces New Data Showing Sustained Immune Remodeling More Than Two Years After Aglatimagene Besadenovec Treatment in Localized Prostate Cancer at ASTRO 2026. News release. Candel Therapeutics. September 30, 2026. Accessed October 6, 2026. https://tinyurl.com/mmpznmmy

3. DeWeese TL, Manzanera A, Sylvester J, et al. Aglatimagene besadenovec (CAN-2409) with radiotherapy for patients with localised prostate cancer: a phase 3, multicentre, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2026;27(6):673-685. doi:10.1016/S1470-2045(26)00071-9