Therapeutic Platforms

Cancer
Cancer is one of the areas where Argos sees the most potential for dendritic cell manipulation and response. Every individual’s cancer is unique. Therefore, the most effective treatment is one customized to a particular disease’s genetic configuration. By capturing the genetic information of tumors, Argos is able to use dendritic cells to trigger a desired immune response.

The Challenge of Cancer: Individual Cancers and Mutations
Genetic mutations and chromosomal abnormalities are commonly associated with human cancers. Unfortunately, since the genetic mutations leading to the development of cancer are often random events, every patient's tumor can contain a unique repertoire of antigens. This characteristic of human cancer requires each patient's immune system be primed to recognize the specific antigens present.

To address the challenge of the unique genetic profile of each cancer, and the genetic mutations of that cancer, Argos is capitalizing on its proprietary capability to make autologous dendritic cell (DC) cancer vaccines. The Argos RNA-loaded DC vaccine is customized to the unique antigenic repertoire of each patient's tumor, equipping the immune system to recognize and fight that particular disease. Because these vaccines include the entire antigenic repertoire of the patient's tumor, they preclude the need to identify or isolate specific tumor antigens. Thus, only Argos vaccines can treat those patients without known tumor antigens or those from whom insufficient tumor material can be obtained, making them suitable for the vast majority of cancer patients.

Creating a Personalized Cancer Vaccine
Argos RNA-loaded DC vaccines start with precursors of the patient's dendritic cells which, when matured for the vaccine, are currently considered the most effective antigen-presenting cells within the immune system. Argos is then able to amplify tumor RNA from the patient, whether from the primary tumor site, distant metastatic sites or from tumor cells present in circulation, and transfect the patient's dendritic cells with the patient's tumor RNA. This process offers the ability for most cancer types at any stage of disease to be target opportunities for the company's cancer vaccine.

Unique Advantages

    • Dendritic cells transfected with RNA-encoding tumor antigens have been shown to stimulate potent immune cell responses equal or superior to other competing approaches
    • The vaccine is completely autologous, potentially offering maximum safety with minimal side-effects
    • The vaccine targets the entire antigenic repertoire of the tumor including ‘private mutations’ unique to that patient
    • A single production run makes enough vaccine to continuously treat the patient for several years
    • Vaccine production requires only a minute tumor specimen, allowing treatment of earlier stage and later stage patients
    • The manufacturing process is optimized for ‘day-old’ monocytes, allowing for centralized manufacturing that provides the flexibility to access patients and clinical sites nationwide
    • Formulation requires no specialized manipulation at the clinical sites, maximizing site participation (thaw in vial, load syringe, inject)

Other Opportunities

Infectious Disease

Chronic viral infections, such as those caused by human immunodeficiency virus (HIV) and hepatitis C virus (HCV), are difficult to treat and often incurable. Argos is exploring the potential to apply its proprietary vaccine process to transfect dendritic cells with patients’ viral RNA antigens, mounting an amplified immune response.

Unique Advantages

    • The vaccine can be comprised of any number of strategically selected viral antigens (chosen to not adversely affect the biology of DCs)
    • Amplification of viral antigens includes patient-specific dominant and quasispecies (important for highly mutagenic viruses such as HIV and HCV)
    • Immune responses generated are 100% relevant for that patient
    • Vaccine production requires only a small plasma sample that can be obtained during leukapheresis
    • If virus escape occurs at some point post-vaccination, the vaccine can be ‘updated’ using a new plasma sample
    • We know of no other DC-based vaccine technology that could feasibly produce an autologous anti-viral vaccine

Autoimmune Disorders
Preliminary research suggests that dendritic cell response may be altered to induce a state of immune tolerance and diminish specific immune responses. The use of such therapy in autoimmune disorders is being explored by Argos, particularly in applications to lupus, an autoimmune disease that results in episodes of varying degrees of inflammation in connective tissues and organs, and for which there is no cure.

Through the study of dendritic cell biology, researchers working with Argos have identified and validated a molecular target (INF-alpha) as a trigger for the onset and maintenance of systemic lupus erythematosus (SLE or lupus).

Transplantation
Patients undergoing solid organ or bone marrow transplant require down-regulation of their immune system to prevent rejection of the transplant. Early research with dendritic cell therapy in transplant recipients has demonstrated a potential role for dendritic cell therapy in preventing organ or graft transplant rejection. Argos is furthering this research effort.