Study: “The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity”
Publisher: Nature
Published date: October 2023
PubMed link to study: https://pubmed.ncbi.nlm.nih.gov/37794185/
Recent research into the PTPN2/PTPN1 inhibitor ABBV-CLS-484 (also known as AC484) reveals promising applications in cancer immunotherapy, by enhancing immune responses to tumors, and also in potentially mitigating chronic inflammation linked to aging. AC484 is an orally bioavailable small-molecule and targets specific phosphatases involved in regulating inflammation. This drug candidate has shown effectiveness in preclinical cancer models, including those resistant to existing therapies. This study highlights the potential dual benefits of AC484 for both oncology and anti-aging, providing a foundational step towards developing therapies that enhance immune function and potentially improve longevity.
ABBV-CLS-484 is being developed by the anti-aging company Calico in collaboration with AbbVie. Read more about Calico here.
Feel welcome to share your own thoughts on this research in the comment section below as well. I will be happy to discuss and learn more about how you see its potential in this field.
Understanding the Role of PTPN2 and PTPN1 in Immune Regulation
The enzymes tyrosine phosphatases, PTPN2 and PTPN1, play crucial roles in regulating inflammation and immune responses within our bodies. They do this by negatively regulating inflammatory pathways by dephosphorylating key molecules involved in immune cell signaling, and thereby dampening various cytokine signaling pathways that are central to the inflammatory process.
By tempering the activity of these enzymes, immune responses can be modulated, which is crucial for controlling chronic inflammation and autoimmunity. Traditionally, these phosphatases have been challenging drug targets due to the chemical nature of their active sites.
The Mechanism and Impact of AC484
The way AC484 works is by targeting these phosphatases and inhibiting the active sites of PTPN2 and PTPN1, thereby enhancing the body’s immune response to cancer cells. This is achieved by amplifying the effects of cytokines like interferons, which are critical for immune cell activation.
In various mouse models of cancer, AC484 has shown to increase the effectiveness of T-cells and natural killer cells against tumors, even in types resistant to other immunotherapies like PD-1 inhibitors. This is particularly significant in cancer treatments where resistance to other forms of immunotherapy, such as PD-1 inhibitors, has been a major hurdle.
Potential Anti-Aging Implications
Chronic inflammation is a significant contributor to the aging process and the development of age-related diseases. This inflammation process is often referred to as “inflammaging”, which is a persistent low-grade inflammation.
By potentially controlling and thereby reducing this inflammation, AC484 could help in mitigating the effects of aging on the immune system. As such enable the maintenance of a more robust immune surveillance as one ages. This aligns with the broader goals of anti-aging research, which seek to not only extend life expectancy but also to improve the health span.
Clinical Evaluation and Future Directions
Currently, AC484 is undergoing clinical trials to assess its safety and efficacy in patients with advanced solid tumors. The outcomes of these trials could pave the way for new strategies in managing cancer and possibly chronic inflammatory conditions associated with aging. Further research will be essential to fully understand the broader applications of PTPN2/PTPN1 inhibition in human health and aging.
You can view the official study details through the following link:
https://www.clinicaltrials.gov/study/NCT04777994?term=NCT04777994&rank=1
In Summary
This ongoing research represents an exciting frontier in the field of immunotherapy and anti-aging, offering insights into how modulating immune responses can help manage both cancer and the natural aging process. As these studies progress, they could lead to significant advancements in our approach to health maintenance in older adults.
