CD70 Immune Checkpoint Molecule for Drug Development

At Creative Biolabs, we have accumulated extensive experience in immune checkpoint-related research, enabling us to provide comprehensive services for our clients. Here, we place a special focus on the CD70-CD27 signaling pathway, an attractive target based on immune checkpoints.

Understanding the CD70-CD27 Signaling Pathway

CD27 is a transmembrane phosphoglycoprotein expressed on CD4⁺ and CD8⁺ T cells, providing co-stimulatory signals to T cells by inducing cell proliferation. As the only known ligand of CD27, CD70 is a strictly regulated type II transmembrane glycoprotein with a molecular weight of 50 kDa, consisting of 193 amino acids.

Fig.1. CD70-CD27 signaling pathway.^1,2

Expression and Function of CD70

During normal hematopoietic development, the expression of CD70 is tightly regulated and limited to activated DCs, B cells, conventional/regulatory T cells, and NK cells. The activity of CD27-CD70 signaling is usually activated under pro-inflammatory conditions. Upon interaction with CD70, cytoplasmic residues of CD27 activate the NF-κB and c-Jun kinase pathways via TRAF2/5, leading to the initiation of various downstream effects:

• Promoting B cell activation and terminal plasma cell differentiation
• Enhancing CD8⁺ T cell activity and promoting TNFα production
• Inducing IFNγ and IL-2 production, thereby increasing NK cell activity

CD70 and Tumor Diseases

Extensive research has validated the dysregulation of the CD70-CD27 axis in tumors, which is associated with tumor progression and immune suppression, exhibiting characteristics contrary to physiological conditions. For instance, abnormal CD70 expression has been observed in glioblastoma, melanoma, and lymphoma:

• In solid tumors, CD70 is exclusively expressed on tumor cells, promoting immune evasion through CD27 expression in the tumor microenvironment.
• In hematologic malignancies, cancer cells co-express CD70 and CD27, promoting tumor stemness, proliferation, and survival.
• CD70 is considered a novel specific tumor marker for renal cancer.

CD70 and Immune Escape

Tumor cells employ various mechanisms to evade detection and elimination by the host immune system, with the CD70-CD27 signaling pathway recognized as an important participant. Three important immune escape mechanisms involving CD70 have been confirmed:

• Chronic co-stimulation leading to T cell exhaustion
• Upregulation of CD95 ligand (CD95L) and/or CD95 induction of T cell apoptosis
• Induction of regulatory T cell (Treg) proliferation

Fig.2. CD70 in tumor environment.^1,2

CD70 Immunotherapy

Due to the abundant expression of the CD70 immune checkpoint in various types of tumors, it has emerged as a promising target for novel tumor interventions. Current CD70 research pipelines primarily focus on phase I clinical trials and involve monoclonal antibodies, antibody-drug conjugates (ADCs), CAR-T therapy, and combination therapies. The mainstream development strategies include:

• Blocking CD70 to eliminate immunosuppression in the tumor microenvironment
• Targeting co-expression of CD27 and CD70 to intervene in survival/proliferation signals in hematologic malignancies
• Killing CD70-positive cancer cells through Fc-dependent complement-dependent cytotoxicity (CDC) and enhanced antibody-dependent cell-mediated cytotoxicity (ADCC)

Services at Creative Biolabs

Creative Biolabs' dedication to constant research and development enables us to stay at the forefront of the immune checkpoint field, pioneering new techniques and methodologies. This empowers us to offer groundbreaking solutions that not only address current challenges but also anticipate future trends. Our proven track record of success, coupled with our relentless pursuit of innovation, makes us the ideal choice for all your immune checkpoint-related needs.

At Creative Biolabs, we invite you to contact us today to collaborate with our team of experts and transform your research goals into reality.

• Custom Immune Checkpoint Protein Development
• Antibody Development for Immune Checkpoints
• Immune Checkpoint Targeted Peptide Development
• Immune Checkpoint Targeted Small Molecule Drug Development
• Immune Checkpoint Assays
• Preclinical Research for Immune Checkpoint Targeting Drugs

References

1. Flieswasser, Tal, et al. "The CD70-CD27 axis in oncology: the new kids on the block." Journal of experimental & clinical cancer research 41.1 (2022): 12.
2. Under Open Access license CC BY 4.0, without modification.

All listed customized services & products are for research use only, not intended for pharmaceutical, diagnostic, therapeutic, or any in vivo human use.