1012P - Intratumoral immunotherapy with a novel TLR1/2/3 agonist, L-pampo, induces robust anti-tumor immune responses and enhances immune checkpoint blockade

Background

Immunotherapy holds the potential to induce potent and durable responses, but few patients respond favorably. Among numerous strategies to enhance the therapeutic efficacy of cancer immunotherapy, Toll-like receptor (TLR) agonist-based approaches have been studied for a long time since they trigger the innate immunity and generate antigen-specific T-cell responses to fight against cancer. Here, we developed a novel TLR1/2/3 agonist, L-pampo^TM, that promotes anti-tumor immunity and enhances immune checkpoint blockade.

Methods

Tumor-bearing mice were intratumorally treated with either L-pampo and/or anti-PD-1 twice a week, and their tumors were measured. The tumors and lymphoid organs were analyzed using flow cytometry, histological, and Nanostring methods.

Results

A potent TLR agonist, L-pampo, was generated by combining a TLR1/2 agonist, Pam3CSK4, and a TLR3 agonist, Poly(I:C). Intratumoral injections of L-pampo suppressed tumor growth in various syngeneic tumor models, namely, MC38 colon cancer, MB49 bladder cancer, and KPC pancreatic cancer. L-pampo promoted CD8+ T-cell infiltration into the tumor, while reducing CD4+ CD25+ FoxP3+ regulatory T-cells. L-pampo also induced robust interferon-gamma secretion from activated T-cells. In bilateral tumor models, intratu moral L-pampo treatment suppressed not only injected tumors but also non-injected tumors, suggesting the activation of systemic immunity by local immunotherapy. L-pampo combined with anti-PD-1 antibody overcame the resistance to PD-1 blockade in non-inflammatory tumors by producing a favorable tumor immune microenvironment.

Conclusions

Overall, our study demonstrated that intratumoral immunotherapy with L-pampo elicits strong anti-tumor immunity within the tumor microenvironment and strengthens the efficacy of immune checkpoint blockade.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

C. Kim, H.J. Chon.

Funding

CHA Vaccine Institute.

Disclosure

Y.K. Heo: Other, Institutional, Funding: CHA Vaccine. B.C. Ahn: Other, Institutional, Funding: CHA Vaccine. H.G. Kang: Other, Institutional, Funding: CHA Vaccine. J.K. Cho: Other, Institutional, Funding: CHA Vaccine. J.S. Yum: Other, Institutional, Funding: CHA Vaccine. All other authors have declared no conflicts of interest.