With the aim to support the drug discovery and development of cellular and gene therapies through a consultation-based and strategic approach with great consideration given to scientific and regulatory issues, Creative Biolabs has established a series of advanced platforms with cutting-edge technologies and innovative solutions to provide T Cell Receptor (TCR) T cell therapy, Chimeric Antigen Receptor (CAR) T Cell Therapy, CAR-macrophage cell therapy, CAR-NK cell therapy.

As a key component in tumor microenvironment, macrophages are actively recruited into tumors and therefore they can be called as tumor-associated macrophages (TAMs). Based on plasticity, macrophages can be divided into classical M1 and alternative M2 type. TAMs closely resemble the M2 type which can accelerate tumor progression. Hence, CAR manipulation to resemble the M2 type into antitumor macrophage will be a promising novel strategy for cancer therapy. Comparing with CAR-T and CAR-NK therapy, CAR-MA owns the following advantages.

• Widely distributed throughout the body;
• Survive in hypoxic and nutrition deficient tumor microenvironment;
• Capability to present antigen as an APC to stimulate adaptive immunity.

Fig.1 Different macrophage types in tumorigenesis. (Aras, 2017)

Chimeric antigen receptors (CARs) are recombinant receptor constructs which are composed of an extracellular single-chain variable fragment (scFv) derived from an identified antibody with high affinity for tumor neoantigen, a hinge or spacer peptide and a transmembrane domain, as well as intracellular signaling domains. Combining the targeting capability for tumor cells with the phagocytosis function of macrophages (see Fig.1), CAR-MA cell therapy shows powerful and promising therapeutic effects for solid tumors where existing CAR-T therapies are facing significant challenges (see Fig.2).

Fig.2 Mechanism of CAR-Macrophage. (Source: from Carisma Therapeutics)

Creative Biolabs has developed an innovative and proprietary platform for next-generation CAR-engineered cell therapies (CAR-Macrophage) with great therapeutic potential for solid tumor (see Fig.3). Our unique and proprietary CAR-MA platform is utilized to manufacture CAR-MA therapies for a wide range of cancers, especially intractable solid tumors. Given to the special characteristics of macrophages, our approach is to use the macrophages isolated from the blood or THP1 macrophage model, and genetically engineer them to express a CAR to guide them to eat the malignant cells. Once CAR-MA preparation is completed, both in vitro assays and in vivo animal testing will be performed to evaluate the efficacy and safety aspects.

Fig.3 Process of CAR-engineered macrophage cell therapy.

End-to-end CAR-MA Integrated Services

With the extensive experience and scientific teams in CAR-T therapy, Creative Biolabs is fully competent and dedicated to our end-to-end CAR-MA therapy solutions for worldwide clients. You can start at any module or choose end-to-end integrated service to best fit your projects within budget requirements.

Neoantigen Identification

With multiple gene and protein analysis technologies, as well as expertise in potential targets with greater potency and lower toxicity, we offer unique de novo neoantigen discovery, identification, selection to get a suitable CAR-MA therapy target.

scFv Generation and Optimization

Empowered by our well-established in-house antibody database and various types of libraries, plus scFv sequencing and affinity measurement platforms, we are committed to generating the optimized scFv with high affinity and good characteristics.

CAR Design & Construction

Sharing the similar components and characteristics of CAR design for CAR-T and CAR-NK, we offer customized CAR design for CAR-macrophage purpose. Specific considerations will be included to fit the needs of macrophage signaling transduction.

CAR-MA Preparation

Given the specific properties of macrophages, to avoid macrophage polarized to the immunosuppressive, pro-tumor phenotype, we developed a unique transfection technology to ensure efficient CAR-MA preparation with desirable anti-tumor phenotype.

CAR-MA In Vitro Validation

For generated CAR-MA product, a broad range of in vitro assays are available to assess the MA function such as CAR expression validation, quantitative phagocytosis and luciferase-based specific killing assays, etc.

CAR-MA In Vivo Testing

After in vitro assays, a series of in vivo testing will be performed in cancer xenograft models to evaluate the pharmacology and toxicology aspects of CAR-MA product.

Fig.4 End-to-end CAR-MA integrated solutions.

Highlights of Our CAR-MA Therapy Program

• End-to-end integrated solutions from bench to bedside;
• Produce cell therapies with enhanced efficacy and potency;
• Commitment with increased safety and minimal toxicity;
• Expertise in regulatory guidelines for streamlined development;
• Extensive knowledge about various solid tumors.

Supported by our multidisciplinary team with flexible solutions, the specific properties of your CAR-MA product will be tailored and flexible customized integration solutions will be provided. Creative Biolabs pioneered the development of CAR-MA platform for the delivery of CAR-MA based medicines that fulfills the stringent requirements of clinical purpose. We are committed to making cell and gene therapy a reality. For detailed information, please contact us to know more.

Reference

1. Aras, S, and Zaidi, M.R. TAMeless traitors: macrophages in cancer progression and metastasis. Br J Cancer. 2017 Nov 21;117(11):1583-1591.

For Research Use Only | Not For Clinical Use