Drug Development Service Targeting Phagocytosis Promotion of TAMs

Targeting Phagocytosis Promotion of TAMs for Cancer Therapy

TAMs, or tumor-associated macrophages, are an essential part of the tumor microenvironment (TME) and play a key role in helping tumor cells create an immunosuppressive milieu. In particular, M2-like TAMs have the potential to be tumor markers for many types of malignancy. Nevertheless, the ability of TAMs to be phagocytosed in tumor tissue is impeded by the existence of phagocytosis inhibitory signals displayed on the tumor cell surface. Thus, recognizing phagocytosis inhibitory signal cues and suppressing their production provide several new thoughts for cancer therapy.

Fig.1 Cancer progression enhanced by M2-like TAMs.¹

Our Drug Development Service Targeting Phagocytosis Promotion of TAMs

Creative Biolabs developed a budget-friendly drug development service targeting phagocytosis promotion of TAMs to assist in cancer therapy drug development. In this service, we design innovative drugs that target the phagocytosis inhibitory signals, with the goal of inhibiting their interaction and promoting TAM phagocytosis. As a full-service provider, we provide multiple types of drug development services including but not limited to the following:

• Antibody drugs development service
• Small molecule drugs development service
• Immune checkpoint inhibitor drugs development service
• Antibody-drug conjugates (ADCs) development service

Fig.2 The development process of phagocytosis inhibitory signals.²

Targets of Our Drug Development Service Targeting Phagocytosis Promotion of TAM

• CD47/SIRPα: Reactivating the phagocytosis of tumor cells by macrophages can be achieved by inhibiting CD47 molecule expression in tumor cells or by preventing the recognition between CD47 and SIRPα. This mechanism effectively impedes the progression of tumors.

• MHC1/LILRB1: On the surface of macrophages, the inhibitory receptor LILRB1 may attach to the β2 microglobulin (β2M) part of MHC I, which is abundantly found on tumor cells. This interaction prevents macrophages from engulfing tumor cells.
• CD24/Siglec10: CD24 is abundantly present on the surface of tumor cells and plays a role in suppressing the phagocytosis of tumor cells by macrophages through binding to Siglec10, which is expressed on the surface of macrophages.

Partnering with Creative Biolabs

Representative Data

DATA 1: Promising cancer immunotherapy strategies that target TAMs to facilitate the killing of tumor cells through cellular phagocytosis have emerged. Through a high-throughput screening of small molecule compounds approved by the US Food and Drug Administration for anticancer purposes, this research has discovered that paclitaxel has the ability to enhance the elimination of lymphoma. This effect is achieved by directly stimulating the phagocytic capability of macrophages. Importantly, this enhancement occurs independently of paclitaxel's cytotoxicity towards NHL cells. The addition of paclitaxel significantly increased the effectiveness of CD47-targeted therapy in treating advanced-stage NHL, resulting in a remarkable improvement in its anticancer properties.

Fig.3 Paclitaxel increased phagocytosis in CD47-deficient Raji cells in a dose-dependent manner.³

DATA 2: Anaplastic thyroid carcinoma (ATC) is widely acknowledged as a highly aggressive variant of human cancer, with a median prognosis of survival ranging from three to six months. Despite the availability of conventional treatment options and targeted therapies, there has been no significant improvement in long-term overall survival. Thus, innovative therapeutic approaches, including immunotherapy, are imperative to address ATC. This study presents evidence supporting the expression of the "don't eat me" signal CD47 on human ATC, and using anti-CD47 alone or in combination with anti-PD-1 mAb immunotherapies could be an invaluable boost to the existing standard of care for patients with ATC.

Fig.4 CD47 inhibition increases phagocytosis of TAMs in human ATC cells.⁴

Creative Biolabs provides this cost-effective drug development service targeting phagocytosis promotion of TAM for global customers to assist in cancer therapy drug development. If you want to know more details about our drug development service targeting phagocytosis promotion of TAM, please don't hesitate to get in touch with us.

References

1. Li, Mengjun, et al. "Targeting tumor-associated macrophages for cancer treatment." Cell & Bioscience 12.1 (2022): 1-13.
2. Liu, Mengmeng, et al. "Targeting macrophages: a novel treatment strategy in solid tumors." Journal of Translational Medicine 20.1 (2022): 1-28.
3. Cao, Xu, et al. "Targeting macrophages for enhancing CD47 blockade–elicited lymphoma clearance and overcoming tumor-induced immunosuppression." Blood, The Journal of the American Society of Hematology 139.22 (2022): 3290-3302.
4. Schürch, Christian M., et al. "Targeting CD47 in anaplastic thyroid carcinoma enhances tumor phagocytosis by macrophages and is a promising therapeutic strategy." Thyroid 29.7 (2019): 979-992.