Safety and feasibility evaluation of first-in-human interleukin-15-transpresenting Wilms' tumor (WT1)-targeting autologous dendritic cell vaccination in cancer patients.

Improvement of first-line treatment for cancer patients with a high tumor recurrence rate and low effective treatment options, such as pancreatic cancer (PC), is warranted. Pancreatic cancer is a devastating disease with a 5-year survival rate below 5%, depending on the specific stage of disease when it is diagnosed, rendering it the 4th most common cause of cancer-related death worldwide. Even those who are eligible for curative-intent resection and conventional adjuvant treatment will nearly all die of their disease due to the high tendency towards recurrence. Adjuvant treatment with gemcitabine after resection of PC decreases recurrence rate, but the disease-free survival of these patients stays dismal with a 5-year survival rate below 21%, underscoring the need for new adjuvant regimens. The combination of gemcitabine with immunotherapy might improve outcome as suggested by some studies, but available data is so far limited to a few early-phase uncontrolled clinical trials. Interleukin (IL)-15-transpresenting dendritic cells (DCs) are a promising armament for immunotherapy of PC. Complementary to current treatments, DCs as quintessential antigen-presenting cells of the immune system can activate the antitumor immune system to attack pancreatic cancer cells. Preclinical data demonstrate the therapeutic potential of these innovative IL-15-transpresenting DCs evidenced by superior activation of the antitumor immune system to attack cancer cells. Since this will be the first-in-human use of IL-15-transpresenting DCs, the objectives are to test the safety, feasibility and immunopotency in patients with refractory solid tumors, the prototypic cancer patient population for phase I trials. This phase I clinical study is pivotal for future testing of this promising IL-15-transpresenting DC vaccine as adjuvant therapy to current anticancer regimens aiming to improve the standard of care of cancer patients with a high unmet medical need.

Keywords:WILMS TUMOR ANTIGEN, CELL THERAPY, CANCER, IMMUNOTHERAPY

Disciplines:Vaccinology, Cancer therapy, Cell therapy, Immunomodulation therapy