Arcelis therapeutic platform

The Challenge of Cancer: Individual Cancers and Mutations

Every individual´s cancer is unique. Therefore, the most effective treatment is one customized to a particular cancer´s genetic configuration. 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 that each patient's immune system be able to recognize and target the specific antigens present.

To address the challenge of the unique genetic profile of each cancer and the genetic mutations of that cancer, Argos' Arcelis personalized immunotherapy technology for cancer captures the complete, unique genetic information of individual tumors, loads a patient's own dendritic cells with the total tumor RNA and uses these dendritic cells to trigger an appropriate immune response. The Arcelis iummnotherapy for cancer, is therefore, customized to the unique antigenic repertoire of each patient's tumor, equipping the immune system to recognize and fight that particular disease. This approach precludes the need to identify or isolate specific tumor antigens and enables targeting of unknown tumor antigens and treatment of patients from whom only a minute amount of tumor material can be obtained.

Creating a Personalized Cancer Product
Argos’ Arcelis immunotherapy for cancer starts with precursors of the patient's dendritic cells, which, when matured for the immunotherapeutic, are currently considered the most effective antigen-presenting cells within the immune system. Argos amplifies whole tumor RNA from each individual patient (whether from the primary tumor site, distant metastatic sites or from tumor cells present in circulation) and then transfects the same patient's dendritic cells with the patient's tumor RNA. This process offers the opportunity for most cancer types at any stage of disease to be target opportunities for the Company's cancer immunotherapy approach.

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 Arcelis immunotherapeutic is completely autologous (derived from the patient’s body), potentially offering maximum safety with minimal side effects
- The Arcelis immunotherapeutic targets the entire antigenic repertoire of the tumor including ‘private mutations’ unique to that patient
- A single production run makes enough product to continuously treat the patient for several years
Production requires only a minute tumor specimen, allowing treatment both of earlier stage and later stage patients
- Argos´ centralized, automated manufacturing process is optimized for ‘day-old’ monocytes, allowing for production 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)

HIV & OTHER INFECTIOUS DISEASES
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 applying its Arcelis technology platform to transfect dendritic cells with patients’ own viral RNA antigens, promoting immune responses perfectly matched to the patient’s unique viral variants.

The Arcelis HIV process utilizes small plasma samples from infected patients to amplify large quantities of messenger RNA that encode selected viral antigens. This technique has the added advantage of amplifying the multitude of patient-specific viral variants evolving in the infected patient, allowing for the creation of a therapy perfectly suited to the individual. Therefore, the viral sequences presented to the immune system to recognize and attack are completely compatible with the virus that has infected the host. The simultaneous presence of autologous viral sequences and dendritic cells should result in a novel immune response, personalized to each patient, that potentially has a greater probability of success in controlling residual virus or a rebound of virus following the cessation of therapy.

Studies published in Nature Medicine and The Journal of Infectious Diseases have demonstrated how patient-specific immunotherapeutic approaches similar to Argos´ have the potential to be effective treatment for people with chronic HIV infection. Additionally, a Phase 1 trial of Argos´ HIV candidate AGS-004, presented at the 2008 International AIDS conference, demonstrated that AGS-004 achieved the trial´s primary endpoint of induction of T cells response to patient-specific HIV antigens. Click here

In October 2006, Argos was awarded a $21M National Institutes of Health (NIH) contract to develop its Arcelis HIV immunotherapy platform. In addition to determining the immunogenicity of the Arcelis HIV product currently in the clinic, the goal of the five-year contract is to subsequently develop then test in the clinic even more potent next generation product candidates.

Argos believes its Arcelis technology can also be used to create immunotherapies for other chronic infectious diseases that don’t respond to current treatments. Infections such as hepatitis C virus (HCV) and herpes represent some of the largest and most significant areas of unmet medical need. In fact, any disease subject to immune surveillance is potentially addressable.

Unique Advantages
- The Arcelis immunotherapeutic can be comprised of any number of strategically selected viral antigens (chosen to not adversely affect the biology of dendritic cells)
- 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
- Production requires only a small plasma sample that can be obtained during leukapheresis
- If virus escape occurs at some point post-treatment, the product can be ‘updated’ using a new plasma sample
- Argos knows of no other dendritic cell-based technology that could feasibly produce an autologous anti-viral immunotherapeutic

created over 15 years ago (26 March 2009)    last modified over 13 years ago (28 September 2011)   [ RDF ]   [ RelFinder ]