Targeting LAG-3 CD223 In Cancer Immunotherapy

Release Date: 07-Feb-2023

The advent of immunotherapy has revolutionized the field of cancer therapy with the goal of harnessing one’s immune system and providing longer lasting cures. Among the existing immunotherapeutic approaches, immune checkpoint inhibitors have shown the most success and adoption by consumers by greatly improving the overall survival rates in certain patient populations. Studies conducted in the area have identified several new immune checkpoint inhibitors, one of them CD223 which is also referred to as lymphocyte activation gene-3 (LAG-3) which has attracted the attention of researchers over the world.


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Due to the wide expression range of CD223 in solid tumors and hematological malignancies, it is being considered as one of the most promising potential therapeutic target. Several pharmaceutical companies have been developing robust clinical pipeline for CD223 inhibition targeting carious cancer subtypes. LAG-3 or CD223 is the third inhibitory receptor which is being tested in clinical trials and has been constantly gardening substantial interest and curiosity among the drug developing community.


The real shift in the market of CD223 targeted therapies was observed when Bristol Myers Squibb entered the industry with the first ever LAG-3 blocking antibody combination, Opdualag for the treatment of unresectable or metastatic melanoma with tumor cell PDL-1 expression lower than 1%. The drug is a first in class immunotherapy combinational treatment of the PDL-1 inhibitor Nivolumab and novel Lag-3 inhibiting antibody Relatlimab. First the US FDA and now the European Commission has granted the commercial nod to the drug based on the results of the clinical trial RELATIVITY-047 which showed that Opdualag had more than doubled median progression free survival in comparison to Nivolumab monotherapy.


The confirming of CD223 to be used as a potential target for immunotherapy caused a new grown interest in the field but it wasn’t until Bristol Myers Squibb came out with a drug that focused on targeting CD223. However, it wasn’t just Bristol Myers Squibb that wanted to exploit the potential therapeutic benefits that CD223 targeting therapies might have, Immutep another global biopharmaceutical company that focuses on cancer immunotherapies was keen to develop its own novel CD223 targeting drugs.


Immutep has succeeded in developing a strong pipeline for CD223 targeting therapies. The company now has the broadest LAG-3 targeting drug portfolio with four product candidates in its clinical channel, 3 of which are in 9 ongoing or planned clinical trials in development for immuno-oncology and autoimmune disease platform. It is now undergoing clinical trials with Merck’s PDL-1 targeting drug Keytruda. On January 2023, Immutep announced that it has successfully enrolled 50% of the planned patinets in the clinical trial evaluating Immutep’s first-in-class soluble CD223 protein Eftilagimond alpha (Efti) in combination with Keytruda as a first line treatment of recurrent or metastatic head and neck squamous cell carcinoma.


Numerous studies have revealed that this target is over expressed on several cancer types’ including non-small cell lung cancer, melanoma, colorectal cancer and others which has made CD223 an ideal target for drug development process. Apart from cancer, researchers have been testing the potential therapeutic application of this novel immunotherapy target CD223 in other diseases like, HIV and autoimmune disorders. For instance, Immutep has started manufacturing process for IMO761, a first-in-class proprietary preclinical candidate, CD223 agonist for autoimmune disease.


The upcoming clinical drug pipeline for novel CD223 drug candidates looks highly crowded. The increasing prevalence of cancer cases and the growing adoption towards emerging CD223 targeting therapies in the pharmaceutical industry, it is foreseeable that the future of this untapped emerging drug target is very flourishing. Some of the key players that are actively working this segment include: Merck, Bristol Myers Squibb, Immutep, Novartis and several others.


This report aims to provide an in-depth analysis on the emerging market of CD223 or LAG-3 targeted therapies. Our report also highlights how the approval of Opdualag by Bristol Myers Squibb generated a sudden wave of developing CD223 antagonists and shifted preclinical studies on the target towards clinical trials. The role of this target beyond its use in cancer immunotherapy is also briefly described in the report. Apart from this, it also provides information about the current market trends and future possible opportunities that might be available in the CD223 targeted therapy market.



Neeraj Chawla

Kuick research

Research Head


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