KEY TAKEAWAYS
- The study aimed to investigate the potential of CD160-TM as a specific tumor target in TNBC patients.
- Researchers noticed that CD160-TM serves as a promising tumor marker for TNBC patients, highlighting the potential therapeutic utility of anti-CD160-TM antibodies.
Despite significant therapeutic progress, triple-negative breast cancer (TNBC) presents a worse prognosis compared to hormone receptor-positive breast cancers, mainly due to molecular and mutational heterogeneity.
Claire Scheffges and her team exacerbated this challenge by using unreliable tumor antigens for specific targeting, hindering efficient tumor cell recognition and depletion. CD160, expressed by NK lymphocytes in two isoforms, namely the GPI-anchored form (CD160-GPI) and the transmembrane isoform (CD160-TM), emerges as a potential candidate for targeted therapy. CD160-GPI, constitutively expressed, plays a role in NK cell cytotoxic activity, while CD160-TM, synthesized upon activation, enhances NK cell killing ability.
They performed an inclusive analysis, evaluating CD160 expression through immunohistochemistry (IHC) on TNBC patient biopsies and flow cytometry on TNBC cell lines. Antibody (Ab)-mediated tumor depletion efficacy was assessed in vitro using antibody-dependent cell cytotoxicity (ADCC) and phagocytosis (ADCP) assays. Furthermore, in vivo experiments were conducted on a TNBC mouse model to validate the therapeutic potential of anti-CD160 antibodies.
About CD160 expression in TNBC patients, IHC analysis on tumor biopsies revealed an atypical CD160 expression pattern. Specifically, TNBC tumor cells exhibited CD160-TM expression, discerned by a conformation-dependent anti-CD160-TM antibody. This contrasted with the absence of CD160-GPI expression. A conformation-independent anti-CD160-TM monoclonal antibody (22B12; muIgG2a isotype) was generated and selected based on predefined specificity and functional criteria.
In vitro functional assays with 22B12 demonstrated the induction of ADCC and ADCP, leading to apoptosis in TNBC cell lines. The conformation-independent nature of 22B12’s activity underscored its efficacy. The in vivo anti-tumor activity of 22B12 was substantiated using a TNBC murine model.
The study concluded that CD160-TM serves as a pivotal tumor marker for TNBC, offering a rationale for utilizing anti-CD160-TM antibodies as effective therapeutic tools in this specific tumor context.
The study is sponsored by INSERM, Université Paris-Cité, The Research Technology National Agency (ANRT), The Research Federative Structure (SFR) Cap Santé, Alderaan Biotechnology
Source: https://pubmed.ncbi.nlm.nih.gov/38360636/
Scheffges C, Devy J, Giustiniani J, et.al (2024). Identification of CD160-TM as a tumor target on triple negative breast cancers: possible therapeutic applications. Breast Cancer Res. 2024 Feb 15;26(1):28. doi: 10.1186/s13058-024-01785-x. PMID: 38360636; PMCID: PMC10870674.
