Cell Therapy Using Monocytes and Macrophages

Updated on Dec 2, 2024 By Dominique Badea, PhD Share

In the scientific discourse around adoptive cell immunotherapy, monocytes and macrophages often take a back seat. For the last two decades, immense time and resources have been spent developing T cell-based cancer therapeutics, such as T cell receptor (TCR) and chimeric antigen receptor (CAR) T therapy. For good reason, these therapies have proven incredibly successful in clinical trials for refractory blood cancers and lymphomas that failed other treatment attempts.

Remembering monocytes’ crucial role in facilitating an effective immune response is essential. Monocytes and their macrophage progeny have been critical components of the immune system’s response to various diseases, particularly cancer. These cells are known for their ability to recruit and activate effector T cells, making them highly versatile and potent in fighting diseases. Monocyte and macrophage cell therapy have recently gained recognition and started receiving the attention they deserve for their potential to bring revolutionary treatments.

Understanding Monocytes and Macrophages

Monocytes and macrophages are key components of innate and adaptive immunity. Monocytes originate from hematopoietic stem cells in the bone marrow, and they circulate in the bloodstream until they are recruited to tissues, where they differentiate into macrophages or dendritic cells.

When they migrate into tissues, monocytes differentiate into macrophages, adapting to their local environment and becoming tissue-resident macrophages (TRMacs) or monocyte-derived macrophages (MoMacs). These subsets are adept at phagocytosis, engulfing and digesting cellular debris, pathogens, and cancer cells. They also orchestrate immune responses by presenting antigens to recruit T cells and secreting various cytokines that modulate inflammation and immunity.

Why Are Monocytes and Macrophages Important?

Both monocytes and macrophages are integral parts of the immune system’s capacity for responding to and eliminating threats. Their ability to transform and adapt enables them to tackle wide-ranging challenges, from infections to tumorigenesis.

Specialized TRMacs are crucial in maintaining tissue homeostasis, repair, and defense in specific tissues like lung or liver macrophages. On the other hand, MoMacs are more commonly associated with inflammatory responses and are essential in wound healing and fighting infections.

The diversity and adaptability of these cells highlight their importance in maintaining health and fighting diseases. Their dual role in directly attacking pathogens and cancer cells and shaping adaptive immune responses makes them ideal targets for therapeutic interventions.

While still in the early stages of development, monocyte and macrophage cell therapy holds great promise for addressing the challenges of cancer and other diseases. Continued research in this field is essential to unlock the full potential of harnessing these natural defenders for therapeutic purposes.

The Potential of Monocyte/Macrophage Cell Therapy

Cell therapy is in a transformative era, with monocytes and macrophages now playing a central role. With their inherent capabilities to initiate, modulate, and execute immune responses, these cells offer fertile ground for therapeutic interventions. Monocyte/macrophage cell therapy leverages these cells’ natural functions, but with a twist—they are engineered or selectively enhanced to target specific diseases—including cancer—more effectively.

Different Types of Monocyte/Macrophage Cell Therapy

The landscape of monocyte and macrophage cell therapy is diverse, with several innovative approaches:

• Blood monocytes: Monocytes are harvested from the patient’s peripheral blood and can be activated or modified before being reintroduced into the body to target and destroy cancer cells.
• Tissue-resident macrophages (TRMacs): Leveraging this macrophage subset involves enhancing their natural tumor-suppressing functions within specific tissues.
• Monocyte-derived macrophages (MoMacs): These are cultured and engineered in vitro before being deployed to infiltrate and fight solid tumors or repair tissue.
• Chimeric antigen receptor-modified macrophages (CAR M): This cutting-edge approach involves modifying macrophages to express chimeric antigen receptors (CARs), which enable them to recognize and kill cancer cells more efficiently. By engineering macrophages with CARs that target specific antigens expressed on cancer cells, researchers aim to enhance the precision and effectiveness of macrophage-based immunotherapy against cancer.

Autologous vs. Allogeneic Monocyte/Macrophage Therapy

Like other types of adoptive cell therapy, monocyte/macrophage therapy can be autologous or allogeneic. Autologous therapy uses the patient’s own cells to minimize immune rejection risks, while allogeneic therapy employs cells from donors to offer ready-to-use therapeutic options.

T cell therapies, especially those utilizing CAR T technology, have made significant headway in treating certain blood cancers, but they rely heavily on the autologous approach to mitigate immune rejection. Natural killer (NK) cell therapy offers a balance, with both autologous and allogeneic options being explored for their natural ability to target cancer without prior sensitization.

However, monocytes and macrophages have many characteristics that make them attractive as an allogeneic therapy. One significant advantage is their reduced likelihood of inducing graft-versus-host disease (GVHD), a potentially severe complication in allogeneic transplantation where the donor’s immune cells attack the recipient’s tissues. Researchers are working on optimizing protocols to derive macrophages from induced pluripotent stem cells that would act as a renewable, allogeneic source of therapeutic cells.

Clinical Advancements and Research

Recent advancements continue to highlight the potential of monocyte/macrophage cell therapy. Engineered macrophages can be directed to solid tumors, where they induce direct cytotoxicity against cancer cells and modulate the tumor microenvironment to support anti-tumor immunity.

Macrophage Therapy Is Better at Attacking Solid Tumors

Macrophage therapy holds significant promise for treating solid tumors. It leverages macrophages’ natural roles to infiltrate and fight cancer. Other immune cells, like T cells, struggle to survive in the tumor microenvironment.

Macrophages naturally migrate towards inflammation and tumor sites, a behavior that can be exploited to deliver therapeutic agents directly into the tumor microenvironment (TME). This homing capability allows targeted therapy, potentially increasing efficacy and reducing systemic side effects.

The tumor microenvironment is critical to cancer progression. Macrophages can have dual roles in cancer, either supporting solid tumor growth (M2-like, tumor-promoting macrophages) or inhibiting it (M1-like, tumor-suppressing macrophages). Therapeutic strategies that reprogram macrophages from a tumor-promoting to a tumor-suppressing phenotype can help modulate the TME in favor of solid tumor suppression and immune-mediated clearance.

Macrophage therapy can also activate other immune system components against cancer cells. By enhancing antigen presentation and pro-inflammatory cytokine production, macrophages recruit T cells and other immune cells to attack the tumor, amplifying the anti-tumor immune response.

CAR Macrophage Therapy

CAR M therapy is a particularly innovative branch of macrophage cell therapy. These trials are pioneering the modification of macrophages to express chimeric antigen receptors, which can specifically recognize and bind to tumor antigens.

By equipping macrophages with these targeting mechanisms, researchers aim to enhance their natural ability to phagocytose cancer cells while potentially activating other immune responses within the tumor microenvironment. Early-phase trials show promising signs of efficacy and safety, marking a significant step forward in applying CAR technologies beyond T cells.

Challenges and Opportunities

While ongoing clinical trials offer promising glimpses into the future of monocyte/macrophage immunotherapy, they also underscore the field’s challenges. Issues such as ensuring targeted delivery, optimizing cell activation, and avoiding off-target effects are at the forefront of current research. Moreover, integrating novel technologies, like better cell separation and activation methods, could enhance these therapies’ efficacy and feasibility.

Benefits of Better Cell Separation and Activation for Monocyte/Macrophage Therapy

The first critical step in preparing these cells for therapeutic applications is isolating monocytes and macrophages from peripheral blood or tissue samples. High-quality cell separation ensures the isolated cells are pure, viable, and functionally intact. This purity is crucial because contaminating cells can interfere with the immunotherapy’s intended mechanisms of action, potentially leading to reduced efficacy or adverse outcomes.

Moreover, high cell viability is essential for the therapy’s success, as more viable cells can lead to a more robust, more effective immune response.

Once isolated, the activation and expansion of monocytes and macrophages are pivotal for maximizing their therapeutic potential. Activated macrophages exhibit enhanced phagocytic activity, improved antigen presentation, and increased secretion of pro-inflammatory cytokines, vital for fighting tumors or facilitating tissue repair.

Revolutionizing Cell Separation With Microbubble Technology

Akadeum’s microbubble technology addresses the challenges of cell separation and activation head-on. By leveraging buoyancy, Akadeum’s microbubbles can selectively isolate monocytes from complex biological samples with high purity and viability without the need for harsh mechanical or chemical treatments that can compromise cell integrity.

Furthermore, Akadeum’s technology can be tailored for specific activation protocols, presenting researchers with a new, exciting tool. By combining cell separation with targeted activation strategies, Akadeum’s microbubbles streamline the preparation of monocytes and macrophages for therapy, enhancing efficacy and reducing the time from sample collection to therapy administration.

Traditional cell separation methods are often expensive and can damage the cells, compromising their therapeutic efficacy. Akadeum’s microbubbles, however, offer a gentle, efficient, and scalable solution for healthier cells.

Meet the Future of Cell Therapy With Akadeum

Collaboration between biotech companies, academic institutions, and clinical researchers is crucial for advancing monocyte/macrophage cell therapy. By sharing knowledge, resources, and technologies, the scientific community can accelerate the development of effective treatments. Akadeum Life Sciences is committed to playing a central role in this collaborative ecosystem.

The journey from bench to bedside is complex and challenging, but the potential rewards for patients and the medical community are unparalleled. We invite clinical researchers and scientists to join us in this exciting endeavor. Together, we can turn the promise of monocyte and macrophage cell therapy into a reality, opening new doors to more effective, personalized, and accessible treatments.

Contact our team of experts today to learn more about integrating Akadeum’s separation, activation, and expansion products into your workstreams.