Long‐term first‐in‐man Phase I/II study of an adjuvant dendritic cell vaccine in patients with high‐risk prostate cancer after radical prostatectomy

Abstract

Background Patients with high‐risk prostate cancer (PC) can experience biochemical relapse (BCR), despite surgery, and develop noncurative disease. The present study aimed to reduce the risk of BCR with a personalized dendritic cell (DC) vaccine, given as adjuvant therapy, after robot‐assisted laparoscopic prostatectomy (RALP). Methods Twelve weeks after RALP, 20 patients with high‐risk PC and undetectable PSA received DC vaccinations for 3 years or until BCR. The primary endpoint was the time to BCR. The immune response was assessed 7 weeks after surgery (baseline) and at one‐time point during the vaccination period. Results Among 20 patients, 11 were BCR‐free over a median of 96 months (range: 84–99). The median time from the end of vaccinations to the last follow‐up was 57 months (range: 45–60). Nine patients developed BCR, either during (n = 4) or after (n = 5) the vaccination period. Among five patients diagnosed with intraductal carcinoma, three experienced early BCR during the vaccination period. All patients that developed BCR remained in stable disease within a median of 99 months (range: 74–99). The baseline immune response was significantly associated with the immune response during the vaccination period (p = 0.015). For patients diagnosed with extraprostatic extension (EPE), time to BCR was longer in vaccine responders than in non‐responders (p = 0.09). Among 12 patients with the International Society of Urological Pathology (ISUP) grade 5 PC, five achieved remission after 84 months, and all mounted immune responses. Conclusion Patients diagnosed with EPE and ISUP grade 5 PC were at particularly high risk of developing postsurgical BCR. In this subgroup, the vaccine response was related to a reduced BCR incidence. The vaccine was safe, without side effects. This adjuvant first‐in‐man Phase I/II DC vaccine study showed promising results. DC vaccines after curative surgery should be investigated further in a larger cohort of patients with high‐risk PC.

Immunotherapy for Prostate Cancer: A Current Systematic Review and Patient Centric Perspectives

“…Other combinations of vaccines including the mRNA variant are being tested with ICIs, including cemiplimab, which is currently approved for skin cancer [ 57 , 58 , 59 , 60 ]. mRNA vaccines are also being combined with androgen receptors and with pembrolizumab [ 61 , 62 , 63 ].…”

Research progress on dendritic cell vaccines in cancer immunotherapy

“…Recently, a long-term first-in-human phase I/II study of an adjuvant DC vaccine in patients with high-risk prostate cancer after radical prostatectomy showed promising results. Among 12 patients with grade 5 prostate cancers, five achieved remission after 84 months, and all mounted immune responses [ 118 ]. As of the end of November 2021, there were 5 ongoing clinical trials with DC vaccines in patients with prostate cancers (Table 3 ).…”

Trial watch: Dendritic cell (DC)-based immunotherapy for cancer

“…These published studies reported results of trials spanning 13 different cancer types, of which the most common were melanoma, 186–189 followed by GBM/glioma, 190–192 prostate cancer, 193 , 194 ovarian cancer, 195 , 196 and pancreatic cancer 197 , 198 ( Figure 1 ). Relative to our previous report in 2019 149 , while the aforementioned tumor types remain well represented, yet we do see a shift from clinical studies focusing on ‘basket trials’ consisting of multiple tumor types, toward specific trials focusing on a particular oncological indication; such that, only two studies enrolled patients with multiple solid tumors, 199 , 200 while another study focused on peritoneal metastases derived from multiple primary malignancies.…”

“…Most of these studies reported the results of clinical trials evaluating autologous DCs pulsed with TAAs or TAA-derived peptides, 188 , 190 , 191 , 193 , 196–199 , 202 , 203 TAA-coding RNAs, 189 , 194 , 204–206 and autologous cancer cell lysates 187 , 192 , 195 , 201 , 207 ( Figure 1 ). This is in line with the ongoing trends in the field, as reported in our previous Trial Watch (February 2019).…”

“…In the above studies, DC vaccination was either assessed as a single adjuvant therapy 187 , 193 , 194 , 196 , 203 , 205 , 206 , 210 (generally following surgery or standard-of-care), or in combination with various conventional anticancer therapies, most often chemotherapeutics 189 , 192 , 195 , 197–199 , 207 , 208 and other standard-of-care regimens 191 , 202 , 204 ( Figure 1 ). Other trials combined DC vaccination with specific immunotherapeutic agents such as ICBs (primarily, anti-PD1 or anti-CTLA4 antibodies) or immunomodulatory monoclonal antibodies (e.g., anti-CD20) 188 , 197 , 199 , 200 , 209 ( Figure 1 ).…”