As shown in the figure above, personalized cancer treatment with a DC vaccine comprises six steps:
(1) Isolation of DC precursor cells (monocytes) from a patient’s blood
(2) Generation of mature DCs
(3) Loading DCs with tumor antigen(s)
(4) Freezing DCs in multiple aliquots for dosing
(5) Quality Control testing and Quality Assurance batch review
(6) Thawing and application of DC vaccine products to patients
Dendritic cell (DC) vaccines are a form of adoptive cell therapy in which modified DCs are used to stimulate a patient's existing immune effector cells to eliminate malignant tumors. In the human body, DCs are responsible for presenting antigens to antigen-specific T cells, causing those T-cells to be activated and proliferate. By modifying dendritic cells to present tumor-associated antigens, this capability can be directed to generate an anti-tumor response.
DC Vaccines and Therapeutic Uses
One of the difficulties associated with the treatment of acute myeloid leukemia (AML) is that a small number of leukemic stem cells (LSCs) may survive induction chemotherapy and later cause disease relapse. The current standard-of-care for maintaining remission after induction chemotherapy is hematopoietic stem cell transplant (HSCT), which is performed infrequently in China as many patients are too elderly, have comorbidities, or lack a suitable donor. As a result, a significant portion of AML patients do not experience long-term disease-free survival after induction chemotherapy. There is accordingly a significant unmet medical need for adjuvant treatments to prevent or delay AML relapse following remission.
Cytovant believes that dendritic cell vaccines are uniquely suited to the prevention of relapse in patients with AML who have undergone induction chemotherapy. Because DC vaccines are designed to activate the body’s own immune effector cells and are administered over a long duration, we believe they are well-suited to preventing relapse caused by LSCs. Through our collaboration and license agreement with Medigene, Cytovant is actively developing a DC vaccine targeting two antigens that are commonly found in AML blasts and LSCs (WT-1 and PRAME).
In a prior Phase 1/2 study conducted by Medigene, 20 patients with AML were treated with this DC vaccine for a period of 24 months following induction or consolidation chemotherapy. Administration of the DC vaccine was shown to be safe and well-tolerated over the 2-year treatment period, and the secondary outcome measures of overall survival rate (OS) and progression free survival rate (PFS) were shown to be 80% (95% CI: 55-92%) and 55% (95% CI: 31-74%), respectively. We believe these data compare favorably with historical standards-of-care, including HSCT and chemotherapy.
DC Vaccine Therapy Flowchart