aAVC is a novel cellular drug in which the mRNA of CD1d molecule and the mRNA derived from cancer (tumor-associated antigen: TAA) or viral antigens are co-introduced into allogeneic cells, and loaded with NKT cell ligand (α-GalCer). This results in the expression of α-GalCer/CD1d complex on the cell surface and cancer or viral antigen protein inside the cells (Figure 1).
The aAVC drug is simultaneously capable of inducing innate (NK/NKT cells) and adaptive (cytotoxic T cells) immune systems (Figure 2). Therefore, it is expected to be a novel type of therapeutic agent. Cancer cells may express or lack the major histocompatibility antigen complex (MHC) and often coexist in the same cancer tissue. Therefore, to kill the cancer cells completely via immunotherapy, activation of both immune systems is required. Notably, aAVCs have the potential to induce long-term memory immunity even after a single administration. With cancer antigen-expressing aAVCs, this long-term anti-tumor effect is expected to provide therapeutic efficacy, prevention of recurrence and inhibition of metastasis.
The first in human, phase 1 investigator-initiated clinical trial of whole WT-1 antigen-expressing aAVC (aAVC-WT1) for refractory and recurrent acute myeloid leukemia (RR-AML) has been completed. The phase 1 clinical trial for AML showed no serious adverse events, confirming its safety as an aAVC platform. As immune responses in humans, we confirmed activation of NK/NKT cells, induction of WT1-specific CD4T cells and CD8T cells, and induction of long-term memory killer T cells. Additionally, we were able to obtain ≥50% reduction in tumor volume (leukemia cells) in about half of the cases, CRi (complete remission with incomplete hematologic recovery) in three cases as proof of concept (POC) of a certain clinical efficacy.
There have been developed products using peptides, mRNA, DNA, cells, and other modalities as cancer vaccines. Compared to other modalities, aAVCs are advantageous as they can induce innate immunity as well as strong acquired immunity. In addition, we verified in the preclinical studies that aAVCs have synergistic effects with anti-PD1Ab, an immune checkpoint inhibitor, in cancer therapy. Furthermore, we do not need to consider specific HLA-restriction in the case of aAVC drug application, indicating that it can be used by anyone.
Peptide and TCR-T-cell therapies can be used for patients with only the specific HLA type. Furthermore, since aAVC does not require autologous cells, it can reduce the burden on the patients compared to other cellular immunotherapies, such as CAR-T or TCR-T cell therapy. In fact, aAVC drugs can be manufactured and stored in large quantities with stable quality as cellular therapeutic agents. These are several advantages of a totally off-the-shelf type of cellular medicine.
The aAVC Drug Translational Unit aims to create therapeutics for cancer or infectious diseases with highly unmet needs using the aAVC platform with its unique features.
The business development office handles alliances for collaboration with companies, universities, and external research institutes. It is also involved in licensing intellectual property rights to companies in collaboration with RIKEN Innovation.
Mission of Translational Research Office (TRO), the competent team which consists of number of experts of translational research (TR) from industry, academic TR institutes, regulatory organizations, is to support projects establishing clinical development plan.
