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One-Stop CAR-MA Therapy Development Solutions

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All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

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Background

Macrophage belongs to an innate immune cell and it is actively recruited into the tumor microenvironment by tumor-derived chemokines. Besides, there are reports saying macrophage represents up to 50% of the tumor mass. Therefore, these properties make it easier to penetrate tumor nodules, which has been challenging for adoptive T-cell techniques. Moreover, macrophages can selectively destroy cancer cells via phagocytosis. In addition, macrophages exert multiple immune effector functions, participating in immune response, e.g. they can directly present antigens to T cells and stimulate an anti-tumor immune response when polarized towards the M1 phenotype. Given the attractive features of macrophages, our approach is to use the macrophages isolated from the blood and genetically engineer them to express a CAR - which means now we tell them what to eat - to set them loose on the tumor to destroy the malignant cells.

Macrophage polarization Fig.1 Macrophage polarization. (Bohlson, 2014)

With the approval of two CAR-T cell therapies in 2017, the CAR-T cell treatment has been a promising tool for the treatment of advanced hematologic malignancies. However, although a lot of CAR-T cell therapies are under preclinical evaluation, this approach has not been proved to be as successful in solid tumors. One of the limitations in solid tumors lies in the poor penetration of T cells into tumors. To address this need, talented scientists from Creative Biolabs turn to genetically engineered CAR-MA, also termed MOTO-CAR, aiming to improve the ability of CAR cells to attack solid tumors.

One-stop CAR-MA Services

Empowered by state-of-the-art technologies and advanced platforms in the field of antibody discovery and immunotherapy, Creative Biolabs offers world-leading chimeric antigen receptor macrophage (CAR-MA) services for solid tumor treatment with academic purposes. With the help of rich experience and scientific teams in CAR-T therapy, Creative Biolabs is confident to offer one-stop serves of CAR-MA including but not limited to:

  • Target Identification & Selection
    We are not only capable of discovering potential targets in solid tumor cells but also good at developing suitable CAR-MA therapy targets with greater potency and lower toxicity.
  • High-Affinity Antigen Binder Generation
    Aided by our well-established antibody discovery platforms, we can obtain high-affinity antibodies in various formats (such as scFv, Fab, VHH) with high specificity by conventional hybridoma technology, powerful phage display technology, and/or advanced native B cell sorting technology.
  • CAR-MA Design & Construction
    Customized CAR constructions are designed for each project. To get over the gene engineering hurdles in using macrophages in adoptive cell therapies, we have developed a unique macrophage gene transfer approach. This novel strategy confers on our CAR-MA a desirable anti-tumor phenotype along with resistance to tumor-induced subversion, which otherwise polarizes non-engineered macrophages to an immunosuppressive, pro-tumor phenotype.
  • CAR-MA Preparation Service
    We also provide CAR-MA production services according to our clients' demands. Various sources of macrophages, including induced pluripotent stem cells (iPSC), human monocytic cell line (THP-1) and human primary macrophages (CD14+ peripheral blood), could be used to construct CAR-MA.
  • Macrophages Activation and Expansion Service
    Macrophages activation is a complex process involving the coordinate/synergistic action of signals from cytokines, chemokines, and pathogen-associated molecular patterns (PAMPs). Activated macrophages undergo many changes which allow them to kill invading bacteria or infected cells. We provide solutions for CAR-MA activation and expansion to support the development of CAR-MA-based immunotherapies.
  • In Vitro Assessments
    Creative Biolabs performs various in vitro assessments, which include CAR expression validation, CAR-MA function measurement, phagocytosis test against target cells, etc. Creative Biolabs has updated a comprehensive set of CAR-MA functional assays to meet your academic or clinical purposes.
  • Preclinical Tests and Clinical Trials
    We are experts in construction animal models for preclinical tests. Both efficacy and toxicity are well evaluated during this stage. Of note, we had several positive results saying the infusion of human CAR-MAs into tumor-bearing mice leads to long-term tumor control and enhanced survival. In addition, clinical project management and execution are also on our list.

Over years in the field of immunotherapy, Creative Biolabs is more than happy to share our technologies, platforms, and experience to facilitate your projects and push the progress towards clinical trials. Please feel free to contact us for more details and our team will get back to you as soon as possible.

Highlights & Advantages

  • Enhanced Tumor Penetration
    Leveraging macrophages' natural ability to infiltrate tumor environments, improving therapeutic efficacy in solid tumors.
  • Selective Tumor Cell Targeting
    Genetically engineered macrophages selectively destroy cancer cells through phagocytosis, ensuring precise and effective treatment.
  • Versatile Immune Functions
    Macrophages present antigens to T cells and stimulate anti-tumor responses, providing a multifaceted approach to cancer treatment.
  • High-Affinity Antigen Binders
    Advanced platforms for generating high-affinity antibodies in various formats, ensuring specificity and potency.
  • Multiple Macrophage Sources
    Use of diverse macrophage sources, such as iPSCs, human monocytic cell lines, and primary macrophages, providing flexibility in therapy development.
  • Comprehensive Service Offering
    End-to-end CAR-MA development services, including target identification, antigen binder generation, CAR design, macrophage preparation, activation, expansion, and in vitro and in vivo assessments.
  • Custom CAR Design
    Tailored CAR constructs for each project, incorporating unique gene transfer methods to enhance macrophage anti-tumor activity.
  • Experienced Team
    Years of expertise in immunotherapy, offering advanced technologies and platforms to facilitate the development of CAR-MA therapies and accelerate progress towards clinical trials.

Resources

Use the resources in our library to help you understand your options and make critical decisions for your study.

InfographicFlyer Support Knowledge
Overview of Chimeric Antigen Receptors

Chimeric antigen receptor (CAR) can combine the extracellular antigen recognition domain from antibodies with the immune cell signaling domain to redirect T cell specificity and induce potent antitumor activity. CAR is an artificial transmembrane receptor that connects the extracellular antigen recognition domain, hinge domain (HD), transmembrane domain (TMD), and intracellular signal transduction domain in series.

Macrophage-based Immunotherapy

Macrophages are vital immune cells involved in phagocytosis, antigen presentation, and cytokine secretion. They originate from circulating monocytes or embryonic development. Macrophages, polarized into pro-inflammatory M1 or anti-inflammatory M2 types, bridge innate and adaptive immunity. They function in defense, immune regulation, and cancer therapy by destroying tumor cells and activating other immune cells. Classified based on tissue of residence and environmental stimuli response, macrophages adapt their roles accordingly. Key therapeutic strategies include monoclonal antibodies targeting macrophages, adoptive transfer of engineered macrophages, and CAR-macrophage therapies. These approaches leverage macrophages' abilities to enhance immune responses and target tumors effectively.

Adoptive Transfer of Macrophages

Macrophages, widely distributed phagocytes, are crucial in innate and adaptive immunity. They develop from either bone marrow-derived monocytes or embryonic yolk sac regions. Adoptive transfer involves transplanting engineered immune cells, including macrophages, to study their therapeutic potential. Macrophage-based immunotherapy uses their phagocytic ability to target tumor cells and activate other immune cells, enhancing anti-tumor effects. CAR-macrophages, genetically modified to express chimeric antigen receptors, directly recognize and phagocytize tumor cells. Examples include HER2-CAR, PSMA-CAR, and EGFRvIII-CAR macrophages, which show promise in clinical trials for various cancers. This approach leverages macrophages' ability to infiltrate tumors, present antigens, and secrete pro-inflammatory factors, offering a synergistic anti-tumor effect. Despite challenges like macrophage plasticity and tumor microenvironment inhibition, CAR-macrophage therapy holds significant potential for cancer treatment.

Related Sections


Reference

  1. Bohlson, S.S.; et al. Complement, c1q, and c1q-related molecules regulate macrophage polarization. Frontiers in immunology. 2014, 5: 402.
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