Correlation analyses suggested that IFNα, TNF, and IL-6 were key for CPG7909-induced LNR-cDC activation, whereas R848's effect appeared more cytokine-independent. We conclude that combining locally delivered CPG7909 and R848 in early-stage melanoma will ensure full-range DC subset activation and robust pro-inflammatory T-cell responses in melanoma SLN, independent of sex.

P2, N=100, Recruiting, Pulmotect, Inc. | Trial completion date: May 2026 --> May 2027 | Trial primary completion date: Apr 2026 --> Apr 2027

In situ immunization with Vidutolimod, a virus-like particle containing a CpG-A TLR9 agonist, has demonstrated anti-tumor activity in pre-clinical and early phase clinical studies, however its effect on tumor-specific CD8⁺ T cells remain poorly defined...Together, these findings demonstrate Vidu treatment expands the number of intratumoral and circulating tumor-specific CD8⁺ T cells, and that the number of tumor specific CD8+ T cells and the anti-tumor response is sustained by the addition of αPD-1. These results support continued evaluation of Vidu as a cancer immunotherapeutic agent, including in combination with immune checkpoint blockade.

P1, N=28, Terminated, M.D. Anderson Cancer Center | Active, not recruiting --> Terminated; <75% participation

P1, N=10, Recruiting, Northwell Health | Not yet recruiting --> Recruiting

These findings indicate BDCA2 plays a dual role in the immune response to Vidu, with the amount of anti-Qb antibody coating Vidu determining whether interaction of Vidu with BDCA2 results in pDC activation or inhibition. This important mechanistic information could influence the design of the next generation of pDC-targeting immunotherapeutic nanoparticles.

P1/2, N=11, Active, not recruiting, University of California, San Francisco | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2025 --> Jun 2026

Here, we developed a novel whole-cell vaccine, termed MDLSD, by combining mitoxantrone (MTX)-induced ICD with the TLR9 agonist SD-101. Furthermore, mice cured by MDLSD developed long-term immunological memory, characterized by a recall response dominated by IFN-γ+ CD8+ and TNF-α+ T cells, enabling rejection of secondary tumor challenges. Collectively, our findings illustrate that the MDLSD vaccine synergizes the antigenic breadth of ICD with potent TLR9 stimulation to elicit robust DC activation, polyfunctional T-cell responses, and durable immunological memory, offering a compelling strategy for cancer immunotherapy.

P1, N=18, Recruiting, NYU Langone Health | Trial primary completion date: Nov 2025 --> Nov 2026 | Trial completion date: Nov 2025 --> Nov 2026

P1, N=140, Recruiting, National Institute of Allergy and Infectious Diseases (NIAID) | Not yet recruiting --> Recruiting

To our knowledge, this study is among the first to evaluate the combination of CpG7909 lipoplexes with anti-PD1 antibodies in the context of cancer immunotherapy. The findings suggest that this approach may convert the TME from an immunologically "cold" to "hot" state, thereby enhancing tumor suppression and potentially improving the response rate to ICIs.

In summary, endosomal TLRa VLPs all have the ability to activate pDCs, however, combined TLR7/8 activation using TLR7/8a VLPs was significantly more effective than the other VLPs at activating T cells and was dependent on direct contact with pDCs. Therefore, TLR7/8a VLPs may potentially induce a robust anti-tumor immune response and warrant further investigation for cancer therapy.