Combination immunotherapy of chlorogenic acid liposomes modified with sialic acid and PD-1 blockers effectively enhances the anti-tumor immune response and therapeutic effects

Abstract

Melanoma is one of the most common malignant tumors. The anti-PD-1 antibody is used for the treatment of metastatic melanoma. Treatment success is only 35–40% and a range of immune-related adverse reactions can occur. Combination of anti-PD1 antibody therapy with other oncology therapies has been attempted. Herein, we assessed whether chlorogenic acid liposomes modified with sialic acid (CA-SAL) combined with anti-PD1 antibody treatment was efficacious as immunotherapy for melanoma. CA-SAL liposomes were prepared and characterized. In a mouse model of B16F10 tumor, mice were treated with an anti-PD1 antibody, CA-SAL, or combination of CA-SAL + anti-PD1 antibody, and compared with no treatment controls. The tumor inhibition rate, tumor-associated macrophages (TAMs) phenotype, T-cell activity, and safety were investigated. We observed a significant decrease in the proportion of M2-TAMs and CD4 + Fop3 + T cells, while there was a significant increase in the proportion of M1-TAMs and CD8 + T cells, and in the activity of T cells, and thus in the tumor inhibition rate. No significant toxicity was observed in major organs. CA-SAL and anti-PD1 Ab combination therapy presented synergistic anti-tumor activity, which enhanced the efficacy of the PD-1 checkpoint blocker in a mouse model of melanoma. In summary, combination immunotherapy of CA-SAL and anti-PD1 Ab has broad prospects in improving the therapeutic effect of melanoma, and may provide a new strategy for clinical treatment.

Phenolic acids and a static magnetic field change the expression of transforming growth factor β isoforms in amelanotic melanoma cells

“…In our previous research, we have already proved the positive effect of chlorogenic and caffeic acid and a static magnetic field on melanoma cells in the aspect of oxidative stress, cell redox homeostasis and apoptosis [ 28 , 33 ]. In turn, Li et al [ 37 ] demonstrated the effectiveness of treatment consisting of a combination of sialic acid modified chlorogenic acid liposome therapy (CA-SAL) in combination with anti-PD1 (anti-programmed death protein 1) antibody treatment. Moreover, the research by Choi et al [ 38 ] also showed the positive effect of Phyllostachys nigra active compounds on melanoma cells.…”

Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials

“…CGA prevents B16F10 melanoma cell proliferation by facilitating the tumor-associated macrophage (TAM) polarization from M2 to M1. CGA with an anti-PD1 antibody can decrease the CD4 + Foxp3 + T cell ratio and increase the CD8 + T cell ratio, leading to an enhancement of immunotherapeutic activity in vivo [289].…”

“…Molecular docking simulation and in vitro kinetic assay [312][313][314][315] Inhibition of α-MSH [312][313][314]; inhibition of tyrosinase [315] CGA [282]; leukemia cell lines U937, and HL60 [284,285]; lung cancer cell line A549 [287]; melanoma C32 and B16F10 [288,289]; glioma cells U87 [290]; osteosarcoma cell lines U2OS, MG-63, and Saos-2 [294,295]; pancreatic carcinoma PANC-1 [297,298]; prostate cancer cell DU145 [300]; and RCC A498 cells [301]; tumor-bearing SCID mouse models [282,287] Increase in p53, Bax, and the ratio of Bax/Bcl-2 [276,277]; blockages of (1) p-STAT-5 and p-CrkL [283,287], (2) the NF-kb pathway [276], (3) the STAT3/Snail pathway [294,295], (4) the PI3K/Akt/mTOR pathway [301], and EMT [276] CGA Cancer management in patients (Section 7.12)…”

Chlorogenic acid: a review on its mechanisms of anti-inflammation, disease treatment, and related delivery systems

“…Albeit various chlorogenic acid isomers exhibit salient advantages over their native counterpart, they occasionally betray certain toxicological concerns and adverse manifestations. Consequently, a panoply of chlorogenic acid encapsulation and delivery stratagems have been envisaged, encompassing liposomes, micelles, and nanoparticles, among others ( Li et al, 2021 ; Li et al, 2022 ).…”