Efficacy of PD-1 Inhibitor Combination Therapy in Non-small Cell Lung Cancer Patients Who Have Not Achieved Major Pathologic Response After Neoadjuvant Immunotherapy: a Multicenter, Phase II Clinical Trial

IBI363 is the worlds first PD-1/IL-2α bispecific antibody fusion protein with an IL-2 arm that has been designed and modified to retain CD25 (IL-2Rɑ) activity to maximize efficacy and high selectivity, and to reduce binding to IL-2Rβγ to reduce systemic toxicity, whereas the PD-1 binding arm allows for blockade of PD-1 and selective delivery of IL-2. Therefore, IBI363 has the ability to simultaneously block the PD-1/PD-L1 pathway and activate the IL-2 pathway, which can more effectively activate tumor-specific T cells. IL-2, as an important cytokine for activating tumor-specific CD8+ T cells, is mechanistically complementary to immune checkpoint inhibitors, and can reverse T-cell depletion, thereby overcoming immune resistance.

LM-108 is a humanized monoclonal antibody targeting the human chemokine CC receptor 8 (CCR8) and is able to modulate the tumor microenvironment by specifically removing tumor-infiltrating regulatory T cells (Treg) through antibody-dependent cell-mediated cytotoxicity (ADCC) without affecting peripheral Treg.

The principle of CTLA-4 combined with PD-1 therapy is to fully relieve the inhibition of T cells by blocking both CTLA-4 and PD-1 immune checkpoints simultaneously.CTLA-4 inhibitors mainly work in the initial immune response stage by blocking the binding of CTLA-4 to B7 and enhancing the activation and proliferation of the initial T cells; whereas PD-1 inhibitors restore the anti-tumor activity of activated T cells by blocking the binding of PD-1 to its ligand PD-L1/PD-L2 and restoring their anti-tumor activity. and its ligand PD-L1/PD-L2 binding, lifting the functional inhibition of activated T cells and restoring their anti-tumor activity. Combination therapy can fully activate T-cells, improve the immune system's ability to recognize and attack tumors, enhance the anti-tumor immune response, and overcome the drug resistance of single therapy, thus improving the therapeutic effect.

Sindilizumab (Sintilimab) is a humanized anti-PD-1 monoclonal antibody that has demonstrated promising anti-tumor activity in several cancer types. It works by blocking the binding of PD-1 to its ligands, PD-L1 and PD-L2, thereby lifting the inhibition of T-cells and restoring the immune system's killing function against tumor cells.