Enhanced antitumor immunotherapeutic effect of B-cell-based vaccine transduced with modified adenoviral vector containing type 35 fiber structures

Abstract

For successful clinical tumor immunotherapy outcomes, strong immune responses against tumor antigens must be generated. Cell-based vaccines compromise one strategy with which to induce appropriate strong immune responses. Previously, we established a natural killer T-cell (NKT) ligand-loaded, adenoviral vector-transduced B-cell-based anticancer cellular vaccine. To enhance tumor antigen delivery to B cells, we established a modified adenoviral vector (Ad-k35) that encoded a truncated form of the breast cancer antigen Her2/neu (Ad-k35HM) in which fiber structure was substituted with adenovirus serotype 35. We observed increased tumor antigen expression with Ad-k35HM in both human and murine B cells. In addition, an Ad-k35HM-transduced B-cell vaccine elicited strong antigen-specific cellular and humoral immune responses that were further enhanced with the additional loading of soluble NKT ligand KBC009. An Ad-k35HM-transduced, KBC009-loaded B-cell vaccine efficiently suppressed the in vivo growth of established tumors in a mouse model. Moreover, the vaccine elicited human leukocyte antigen (HLA)-A2 epitope-specific cytotoxic T-cell responses in B6.Cg (CB)-Tg (HLA-A/H2-D) 2Enge/Jat mice. These findings indicated that the Ad-k35 could be appropriate for the preclinical and clinical development of B-cell-based anticancer immunotherapies.

IL21 Therapy Combined with PD-1 and Tim-3 Blockade Provides Enhanced NK Cell Antitumor Activity against MHC Class I–Deficient Tumors

“…Advances in cancer immunotherapy are not only changing standard therapies for cancer but are also expected to yield complete responses in patients with advanced cancer (25)(26)(27). Although various cancer immunotherapies, such as checkpoint inhibitors, immunostimulatory cytokines, tumor vaccines, and CAR-T cells, have shown clinical efficacy, a significant proportion of cancer patients still do not respond to any of these immunotherapies (28)(29)(30). Most immunotherapies have mainly focused on their effect on T cells, whereas NK cells are one of the most important effector arms, especially against MHC class I-deficient tumors, whose frequency is closely associated with the malignancy of the cancer (4,5,31,32).…”

IL-21-mediated reversal of NK cell exhaustion facilitates anti-tumour immunity in MHC class I-deficient tumours

“…centrifugation step at room temperature, and the cells were subsequently incubated for an additional 18 h (for the B/Mo/αGC preparation this step was skipped). αGC (KRN7000, Enzo Life Science, Japan) was loaded into the prepared B cells and monocytes for NKT activation based on our previous studies20212251.…”

Tumor-Derived Osteopontin Suppresses Antitumor Immunity by Promoting Extramedullary Myelopoiesis

“…To this end, we employed a B-cell-based antitumor vaccine (31,32). We have convincingly showed that a NKT ligand-loaded, B-cell-based vaccine elicits tumor-specific immune responses (21,33,34). We subcutaneously inoculated Balb/c mice with CT26 tumor cells on day 0 and then intraperitoneally injected the mice with 0.5 mg of antiosteopontin (MPIIIB10) or mIgG as a control every other day for 10 days (Fig.…”