Therapeutic Platforms: Cancer and HIV

The Challenge of Cancer: Individual Cancers and Mutations
Every individual´s cancer is unique. Therefore, we believe that 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 tumor RNA and uses these dendritic cells to trigger an appropriate immune response. The Arcelis immunotherapy 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 small amount of tumor material can be obtained.

The Argos’ Arcelis personalized immunotherapy technology optimizes treatment to fight the current manifestation of each patient’s particular disease.

Creating a Personalized Cancer Product
Argos’ Arcelis immunotherapy for cancer starts with precursors of the patient´s dendritic cells, which we believe when matured for the immunotherapeutic, are 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.

In January 2013, Argos Therapeutics announced enrollment commencement for the ADAPT Phase 3 clinical study for AGS-003, an investigational, fully personalized, dendritic-cell based immunotherapy. AGS-003 is being examined in combination with standard targeted drug therapy versus standard therapy alone, for the potential to extend overall survival for newly-diagnosed, unfavorable risk metastatic renal cell carcinoma (mRCC) patients. To create AGS-003, ribonucleic acid (RNA) is isolated from a small tumor sample obtained from standard tumor removal surgery (nephrectomy) or surgical biopsy (metastasectomy), and the patient´s dendritic cells are taken during a single leukapheresis procedure. The tumor RNA is used to “program” the dendritic cells with the entire disease-antigen repertoire to trigger an immune response against the patient´s specific cancer. These antigen-loaded dendritic cells are then formulated into a ready-to-use, intradermal injection. For more information about AGS-003 and the ADAPT study, visit

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 has developed an automated manufacturing process and a single manufacturing facility that can support commercialization for North  America, 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)

The Arcelis immunotherapeutic approach targets a patient´s complete antigenic repertoire, including “private mutations” unique to that patient.

HIV & Other Infectious Diseases

The Challenge of Cancer: Individual Cancers and Mutations
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 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 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 treatments 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. For further information see the following site at

In September 2006, Argos was awarded an National Institutes of Health (NIH) contract to develop its Arcelis HIV immunotherapy platform. Under this contract, as amended, the NIH has committed to fund up to a total of $39.3 million. Argos is using the funds from the contract to develop AGS-004, including funding all the costs of the phase 2b clinical trial of AGS-004. 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 HCV and herpes represent some of the largest and most significant areas of unmet medical need. In fact, Argos believes any disease subject to immune surveillance is potentially addressable.

Unique Advantages

  • The Arcelis immunotherapeutic treatment 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 and a single 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

In addition to its dendritic-cell immunotherapy programs, Argos broadens its therapeutic focus to transplantation and autoimmune disorders.

Programs in Transplantation and Inflammatory and Autoimmune Disorders

In addition to its Arcelis technology, Argos has leveraged its expertise in the biology of dendritic cells to develop additional novel technologies with applications for organ and tissue transplantation and inflammatory and the treatment of autoimmune disorders.

The Company is developing AGS-010, a soluble recombinant protein — CD83 — shown to be an effective immunosuppressant in several mouse model systems. Dendritic cells treated with CD83 are able to induce regulatory T cells, which are responsible for immune tolerance to foreign or self-antigens, illustrating the protein’s potential applications to inflammatory and autoimmune diseases and transplantation rejection.

Preliminary data suggest that CD83 can be developed to treat multiple sclerosis, irritable bowel disease and transplantation rejection. Strikingly, CD83 distinguishes itself from immunosuppressants, whether FDA approved or in development, in that it does not appear to require chronic administration and does not leave the patient globally immunosuppressed.

Argos received a $1 million grant from the Alliance for Lupus Research to develop a monoclonal antibody-based therapy for the treatment of systemic lupus erythematosus (SLE). Argos identified and validated a molecular target — Interferon-alpha — as a trigger for the onset and maintenance of SLE, and as having a role in the onset of psoriasis. Argos has tested an anti-Interferon-alpha monoclonal antibody, AGS-009, in a phase 1 clinical trial in SLE patients.