Reprogramming Tumor-associated Macrophages (TAMs) with Anticancer Therapies

Creative Biolabs has established a cutting-edge Platform for macrophage development. Our experienced in-house expert team of tumor-associated macrophage (TAM) reprogramming is committed to providing high-quality TAM reprogramming services by a combination of chemotherapies and immunotherapies. Our multidisciplinary scientists will work together closely to address these scientific and technical challenges.

Background of Reprogramming TAMs

TAMs are the most abundant leukocyte subset in many cancers and play a major role in the creation of a protective niche for tumor cells. Their ability to generate an immune-suppressive environment is crucial to escape the immune system and to allow the tumor to proliferate and metastasize to distant sites. TAMs presenting an M2-like polarization, inhibit immuno-stimulatory signals and lack cytotoxic activity, therefore promoting tumor development and survival. TAMs are promising targets for novel anti-tumor treatments. Chemotherapy, radiotherapy, and novel immunotherapies based on immune-checkpoint inhibition are often not able to limit cancer growth due to the presence of pro-tumoral TAM. Several novel therapeutic approaches have been implemented to deplete TAMs in tumors. however, more recent approaches are majorly focused on the usage of TAMs themselves to fight cancer. Reprogramming of immune-suppressive and pro-tumoral macrophages (M2-like) into immunostimulatory and anti-tumor cytotoxic effector cells (M1-like) is expected to reconstitute a reactive immune system with the ability to fight and eliminate cancer in the patient.

Fig.1 Summary of available therapeutic strategies to target TAMs.^1,2

Reprogramming TAM with Anticancer Therapies at Creative Biolabs

Creative Biolabs has organized a staff of outstanding scientists who have engaged in TAM reprogramming for many years. By leveraging the wealth of information that we have on TAM reprogramming, we provide our clients with highly customizable solutions. Immunotherapies and chemotherapies could be used to reprogram TAMs into M1-like macrophages. Combination of chemotherapies, such as chemical compounds, and immunotherapies, such as Toll-like receptors (TLRs), stimulator of interferon genes (STING) agonists, and monoclonal antibody (mAbs), targeting macrophage reprogramming could also synergize their effects on tumor regression.

• Chemical compounds
  Another alternative to reprogram TAMs is the use of different chemical compounds. IFNγ, vadimezan (DMXAA), plasma protein histidine-rich glycoprotein (HRG) and metformin have been found to repolarize macrophages in M1 phenotype.
• TLR agonists
  TLRs are innate immunity pattern recognition receptors also expressed by including macrophages, which play a key role in orchestrating the immune response. TLR agonists represent a promising antitumor therapy and have been used to stimulate M2-like or tumor-conditioned macrophages towards an M1-like antitumoral phenotype.
• STING agonists
  As a cytoplasmic DNA sensor anchored in the endoplasmic reticulum, STING has been used to reprogram TAMs through activation of IRF3 and type I interferon (IFN) genes.
• mAbs
  Several mAbs, such as anti-CD40 mAbs and anti-CSF-1R mAbs, have been investigated to reprogram TAMs resulting in an effective antitumoral activity. The combination of anti-CD40 with anti-CSF-1R impairs the recruitment of new TAMs towards the tumor.

With industry-leading expertise and state-of-the-art equipment, the scientific team at Creative Biolabs has the necessary expertise and capabilities to provide overall solutions for TAM reprogramming, focusing on innovative research. For more detailed information, please feel free to contact us and further discuss with our scientists.

References

1. Anfray, Clément, et al. "Current strategies to target tumor-associated-macrophages to improve anti-tumor immune responses." Cells 9.1 (2019): 46.
2. Under Open Access license CC BY 4.0, without modification.