Regimens of Immune Checkpoint Inhibitors in Combination with ADCs

In recent years, several immune checkpoint inhibitors have shown promising therapeutic results. However, many problems have also been shown. With the maturation of ADC technology, combination regimens of immune checkpoint inhibitors in combination with ADCs are showing therapeutic potential.

Currently, immune checkpoint inhibitors in combination with ADCs are being favored by major pharmaceutical companies. Creative Biolabs, as an expert in the field of immune checkpoint research, introduces some regimens of immune checkpoint inhibitors in combination with ADCs and provides customized services.

Therapeutic Potential of Immune Checkpoint Inhibitors in Combination with ADCs

• ADC drugs piggyback on cytotoxic drugs, such as microtubule protein inhibitors and topoisomerase inhibitors, which can directly activate and promote the maturation of dendritic cells. This implies that there may be an immune-activating function of ADCs and a synergistic effect with immune checkpoint inhibitors.
• Also, immune checkpoint inhibitors enhance the activity of ADC drugs.
• Clinical trial data from several cancer types have shown that anti-PD-1 monoclonal antibodies in combination with ADCs demonstrate better efficacy, and the potential synergistic effect between the two can overcome the resistance when they are used alone.

PD-1/PD-L1+ADC Therapy

Overall, immune checkpoint inhibitors, represented by anti-PD-1/PD-L1, have taken an important role in antitumor therapy, and due to the limited efficacy of single agents, combination therapy has become a major strategy.

• For uroepithelial cancer
  Nectin-4 is a cell adhesion molecule, a type I transmembrane protein encoded by NECTIN4 of the Nectin family, which is highly expressed in uroepithelial cancers and plays a key role in tumorigenesis, invasion, and metastasis. ADC targeting Nectin-4, in combination with an anti-PD-1 monoclonal antibody drug, has been approved for the first-line therapeutic indication of uroepithelial cancer.
• For non-small cell lung cancer
  TROP2 is a transmembrane glycoprotein that is overexpressed in several types of solid tumors. An ADC targeting TROP2 consists of a humanized anti-TROP2 monoclonal antibody coupled to DNA topoisomerase I inhibitor via a stable tetrapeptide-based cleavable junction. Combination with anti-PD-1 monoclonal antibodies is more effective in the treatment of advanced or metastatic non-small cell lung cancer (NSCLC).
• For cervical cancer
  TF is a cell surface protein that is highly expressed on a variety of solid tumors, including cervical cancer, and is associated with tumor growth, angiogenesis, metastasis, and poor prognosis. An ADC targeting TF in combination with an anti-PD-1 monoclonal antibody for the treatment of cervical cancer has been studied to evaluate its safety and efficacy.
• For triple-negative breast cancer
  Combination therapy with anti-PD-L1 inhibitor and HER2 ADC for locally advanced or metastatic triple-negative breast cancer showed better efficacy. The combination of ADC targeting LIV-1 and anti-PD-L1 monoclonal antibody showed some degree of shrinkage of tumor lesions in most patients.

Numerous related trials are still underway. Creative Biolabs provides related research services to assist scientists in achieving early positive results.

References

1. Müller P, et al. Combining ADCs with immuno-oncology agents. Innovations for next-generation antibody-drug conjugates, 2018: 11-44.
2. Saini K S, et al. Antibody-drug conjugates, immune-checkpoint inhibitors, and their combination in breast cancer therapeutics. Expert Opinion on Biological Therapy, 2021, 21(7): 945-962.
3. Gerber H P, et al. Combining antibody–drug conjugates and immune-mediated cancer therapy: what to expect? Biochemical pharmacology, 2016, 102: 1-6.

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