The founding scientists behind Edinburgh-based Macomics, Dr Luca Cassetta and Professor Jeff Pollard who have led the field in understanding the role of macrophages in development, tissue repair and cancer, have authored a major Perspectives review in Nature Reviews Cancer¹, detailing the seminal discoveries in macrophage biology over the past 50 years revealing exciting future prospects for developing precision medicines to modulate macrophages for the treatment of cancer by targeting tumour associated macrophage (TAMs) in the tumour microenvironment (TME).
The TME is now recognized to be inundated with immune cells, of which TAMs are often the most abundant by cell number. TAMs were initially thought to be antitumoral, although some experiments suggested that they could enhance tumour cell growth. However, with the advent of new technologies, sophisticated mouse models and human clinical sample analysis, the roles of TAMs were revealed.
Clinical correlative data and a plethora of preclinical studies of cancers have now shown that both tumour-associated and metastasis-associated macrophages play an important role in promoting cancer.
Scientists are still in the process of understanding TAMs heterogeneity including the cellular interactions during tumour progression and in response to therapy, but Improved intravital imaging (IVI) capabilities in preclinical models and newer technologies such as spatial transcriptomics and multicolour multiplex immunofluorescence and mass spectrometry are enabling mapping at single-cell resolution in the TME cellular landscape.
As summarized in the review, myeloid targeting strategies are now in the clinic and show early signs of efficacy as mono and combination therapies.
“We are entering a golden era of discoveries, resulting in the manipulation of the TME, and in particular TAM biology, that will allow immunotherapy to be widely applicable to many if not all cancers”, conclude Dr Cassetta and Prof. Pollard, adding “Recent technological advances have enabled the decoding of TAM complexity in human tumours; such important steps will allow a more precise TAM targeting in the clinic. The next big challenge will be to apply these technologies on clinical samples coming from patients who failed previous cancer therapies to assess TAM evolution during cancer treatment resistance.”
Macomics is an immuno-oncology company set up to take forward these learnings and opportunities.
Prof. Pollard is a Principal Investigator at the MRC Centre for Reproductive Health (MRC-CRH), University of Edinburgh. Formerly its Director, he has been investigating the roles of macrophages in development, tissue repair and cancer for almost 30 years. His group was the first to show that tumour-associated macrophages promote the progression of tumors to metastasis in part, through the establishment of a suppressive immune microenvironment that supports tumor cell survival. He is co-founder of and remains advisor to Macomics. Dr Cassetta previously worked with Prof. Pollard and is now VP immunology at Macomics, having left his role at the University of Edinburgh to join the company full time.
Modulating TAMs can alter the tumour microenvironment enhancing the body’s ability to fight cancer. The tumour microenvironment changes macrophage behaviour, and Macomics is exploiting disease-specific TAM biology to selectively target these immunosuppressive cells.
It has proprietary cell models and approaches for the genetic manipulation of macrophages that, when combined with novel cell functional assays and informatics, enables new target opportunities for specific therapeutic hypotheses to be revealed.
Macomics portfolio is diversified by the mechanism of action and is focussed on multi-hit biological hypothesis, modulating both TAM biology directly and the activity of the broader immune system, to re-invigorate immune responses against cancer cells. It will continue to expand its portfolio of validated targets in diseases where macrophages play a central role in aetiology, response to therapy, and patient outcomes.
Dr Steve Myatt, Macomics CEO said
“We have built a world-class team and made great progress based on the discoveries by our pre-eminent scientists in the field of macrophage biology whose unparalleled expertise guides our mission to discover new therapies that improve the long-term outcome for cancer patients. We are passionate about the therapeutic potential of targeting macrophages for the treatment of cancer. Our vision is to develop a new approach to targeting the immunosuppressive tumour microenvironment, that exploits disease-specific macrophage biology to harness the power of the entire immune system. Our diversified portfolio of antibody programs combined with our proprietary target identification approach and world-class team uniquely positions us to deliver on this vision.”
- Cassetta, L., Pollard, J.W. A timeline of tumour-associated macrophage biology. Nat Rev Cancer(2023). https://doi.org/10.1038/s41568-022-00547-1