QL1706 (Aipalolimab/Tuvonralimab): A First-in-Class PD-1/CTLA-4 Bispecific Combination Antibody Leveraging the Proprietary MabPair™ Platform for Enhanced Efficacy and Safety in Solid Tumors

MabPairTMThe innovation of the technology platform lies in its unique cell line screening and gene engineering strategy. The platform selected the CHO-S™ cell line G19G4-4B4 clone, which is highly effective in producing anti-PD-1 antibodies, and ingeniously introduced the heavy and light chain expression genes of the anti-CTLA-4 antibody. Through extensive cell screening, a stable2:1 Fixed RatioHigh-expression anti-PD-1 and anti-CTLA-4 monoclonal antibody cell lines provide an ideal cellular foundation for production. Additionally, MabPairTMThe platform has made precise modifications to the interface residues of heavy chain/heavy chain and heavy chain/light chain, introducing uniquely designed heavy chain pairing keys and light chain pairing keys. This innovative measure effectively avoids the generation of mismatched components, ensuring the uniformity and stability of the final product.

It can be said that MabPairTMThe technology platform not only makes it possible to implement the innovative dual-action mechanism of QL1706 but also provides a solid guarantee for its stability and safety in clinical applications. The use of this platform marks an important step forward in the field of cancer immunotherapy regarding precise control and personalized treatment.

For dual immunotherapy based on immune checkpoint inhibitors such as PD-1 inhibitors + CTLA-4 inhibitors, how to balance immune activation with adverse reactions has always been an urgent issue in this field. The innovation of the Aito combination antibody lies in its precisely regulated dual mechanism of action and the innovative MabPair technology.TMApplication of Technology Platform.

Aipalolizumab, the anti-PD-1 component in the combination, adopts the more mainstream lgG4 backbone.Avoided ADCC and CDC effects，Thereby protecting activated CD4+ and CD8+ T cells from depletion. This design helps maintain the long-term survival and functionality of T cells while generating higher concentrations of interferon-gamma (IFNγ) in the tumor microenvironment, thus enhancing the tumor-killing ability of T cells.

Tovorali单抗，作为组合中的抗CTLA-4部分，扮演着至关重要的角色。CTLA-4作为一种免疫检查点分子，在T细胞的激活过程中起到抑制作用。Tovorali单抗的lgG1抗体骨架设计，使其在与调节性T细胞（Treg细胞）表面的CTLA-4结合后，Trigger Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) Effect, Depleting Treg cells that suppress tumor immune responses to enhance anti-tumor efficacy. In addition, to further improve efficacy and safety, TovorolizumabThe Fc segment has been carefully re-engineered to reduce its binding affinity to FcRn, thereby shortening the drug's half-life to one week.This change ensures efficacy while...Reduced the adverse reactions that may be caused by prolonged CTLA-4 suppression。

The combination of these two monoclonal antibodies in the Aito combination antibody creates a powerful synergistic effect. By effectively lifting the suppression on T-cell activation, maintaining the activity and proliferation of effector T cells, and further killing Treg cells, it achieves the effect of improving the tumor microenvironment, thereby forming a positive feedback loop within the cancer-immunity cycle.

In summary,The Aito combination antibody, based on its unique dual mechanism of action, simultaneously binds with MabPair.TMThe precise control of the technology platform has achieved the goal of enhancing efficacy and reducing toxicity.。This innovative combination antibody provides a new perspective for tumor immunotherapy and also brings new hope to patients. With the continuous advancement of clinical research, the Aito combination antibody has demonstrated excellent efficacy and safety in various solid tumors.

In Phase 1 clinical studies, the combination of Aituo antibodies got off to a good start, demonstrating good safety and tolerability. In 518 patients with advanced tumors who had failed traditional treatments,Only 8.1% of patientsExperienced grade 3 or higher immune-related adverse events, highlighting the significant safety advantages of the Aito combination antibody.

In patients with recurrent or metastatic cervical cancer, the pivotal Phase II registration study of the Aito combination antibody achieved remarkable results, with an ORR of 33.8% in second-line systemic treatment.Median PFS reached 5.4 months. This breakthrough not only ignites a new ray of hope for cervical cancer patients, but based on this data, the Aito combination antibody has also submitted an application for marketing approval. Subsequently, the 202/204 studies once again confirmed that moving the Aito combination antibody to first-line treatment can also bring significant clinical benefits to patients, regardless of their PD-L1 CPS status. The ORR of Aito combination antibody combined with chemotherapy ± bevacizumab was as high as 76%.

In the treatment of patients with EGFR-mutated non-small cell lung cancer (NSCLC) who have developed resistance, the Aito combination antibody has also demonstrated significant efficacy.Median PFS reached 8.5 months. In the first-line treatment of liver cancer,Aito Combination AntibodyThe combination regimen with bevacizumab achieved a 38.3% response rate., once again demonstrating its great potential in improving clinical benefits for patients.

It is not difficult to see that the therapeutic potential of the Aito combination antibody has already been demonstrated in various solid tumors such as cervical cancer, non-small cell lung cancer, and liver cancer. This undoubtedly indicates that it will become an important new option in the field of cancer treatment. Currently, Phase I-III clinical studies related to the Aito combination antibody are being conducted across more types of tumors, including renal cancer, colorectal cancer, and nasopharyngeal cancer, in addition to the three tumor types mentioned above. The treatment strategies involve its combined application with other treatment methods such as chemotherapy, targeted therapy, and radiotherapy. It is believed that as these studies progress, the Aito combination antibody is expected to provide innovative and optimized solutions for more cancer patients, bringing better clinical benefits.

With a deeper understanding of the mechanism behind the Aito combination antibody, we are able to glimpse the full scope of this innovative therapy. Known as the "Aito Double Strike," this combination antibody not only carries an innovative dual immune checkpoint inhibition mechanism but also leverages MabPair.TMThe world's first application of the technology platform has injected new vitality into the field of cancer treatment. "Qi Hu Life" vividly illustrates the clinical efficacy of Aito combination antibody, which has achieved unprecedented efficacy in cervical cancer, non-small cell lung cancer, liver cancer and other types of tumors. It not only brings real clinical benefits to patients, but also points the way for future cancer treatment.

Currently, on the hopeful yet challenging path of exploring cancer treatments, the story of the Aito combination antibody has just begun. This innovative drug not only represents a new method of treatment but also symbolizes a steadfast belief in fighting cancer and safeguarding lives. Looking ahead, as research on the Aito combination antibody continues to deepen across various tumor types, we anticipate that it will offer more patients innovative and optimized treatment options, continuing to create more life miracles.

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