Immunotherapy, Vaccines and Virotherapy

Overall Scientific Area

The Biodesign Institute at ASU harnesses the talents of innovative people and multi-disciplinary resources to solve major problems based on biological principles. The general scientific direction of B-CIVV is to invent, develop, and translate novel therapeutic strategies against cancer and infectious diseases. B-CIVV is crafting next-generation treatment strategies in the areas of vaccines, engineered viruses and bacteria, and immune-based therapeutics.

Structure of B-CIVV

There are two parallel B-CIVV research divisions, each devoted to developing novel therapeutic strategies against specific disease targets: 1- Division of Immunology and Cancer (DIC), and 2- Division of Infectious Diseases (DID). Scientists from both within and outside Biodesign are appointed as either Primary or Associate Faculty members of B-CIVV. In general, Primary members will have their lab space within the Biodesign Institute, and Associate members are physically located outside the Biodesign Institute or have their Primary affiliation with another Center at Biodesign.

(1) B-CIVV Division of Immunology and Cancer (DIC)

The field of cancer therapeutics is currently undergoing a revolution as biologic-based treatment modalities are being developed, and a host of novel immuno- and viro-therapeutics to treat cancer are in varying stages of development and licensure. Moreover, many of the biologic activities of this new generation of therapeutics are being defined in experimental model systems. Amongst these developments include: A- cancer-specific oncolytic viruses (eg T-Vec, developed by Amgen Corp) that replicate selectively within tumor beds to thereby promote more robust anti-tumor immune responses; B- drugs and antibodies that modify key immune pathways (eg immune checkpoint inhibitors); C- strategies that re-program cancer patient lymphocytes to better recognize and kill cancer targets (eg CAR-T cells); and D- various combination strategies (eg “oncolytic vaccines”) that exploit vaccination modalities against tumor antigens along with other immunotherapeutic enhancements. The following scientific areas are of special interest to the B-CIVV DIC:

  1. Oncolytic virotherapy and viral vectors

  2. Tissue-specific and leukocyte-specific engineering

  3. Tumor tissue microenvironments

  4. Anti-cancer vaccines, immunotherapy and tumor-targeting reagents
     

(2) B-CIVV Division of Infectious Diseases (DID)

The field of infectious disease is very broad, and B-CIVV focuses on discoveries and intervention strategies that also have wide implications. For example, the White House recently released a national action plan for combating antibiotic-resistant bacteria that includes: A- prevention and containment of antibiotic-resistant infection outbreaks; and B- development and deployment of next-generation diagnostics, antibiotics, vaccines, and other therapeutics. Moreover, a recent British study showed that by 2050, antibiotic resistance could become more deadly than cancer. DID will provide new paradigms for infectious disease prevention, control, and treatment through a systems-wide understanding of the dynamic interactions between the pathogen, the host, and the microenvironment and through the development of applied and novel therapeutic and diagnostic strategies. We are entering an era that demands an integrated study of biological systems with bioinformatics, computational biology, engineering, and physics as the prevalent concept in contemporary infectious disease research. To fully understand the complexity of host-pathogen interactions that leads to infectious disease, B-CIVV applies novel approaches beyond current conventional methodologies to unveil the dynamic relationships within their appropriate biological contexts. DID in particular provides an innovative platform to enable paradigm shifts in our understanding of the biological, biochemical, and biophysical basis of infectious diseases and associated factors influencing the interplay between pathogens, their hosts, and the microenvironment.  These advanced platforms include predictive model systems that mimic the inherent context and complexity at the interface between the host and microorganisms (pathogens and commensals), and includes state-of-the-art imaging systems to track cells and tissues in real time. This novel, interdisciplinary approach will lead to revelations in our understanding and methodologies for the control and treatment of clinical, animal and agricultural infectious diseases, including those caused by emerging and re-emerging pathogens that are multidrug resistant. 

B-CIVV Imaging Core

As a component of the infrastructure for B-CIVV, a support equipment Facility Imaging Core focuses on imaging modalities for in vitro and in vivo models, tracking specific cell types and tissues, signal transduction pathways, and instrumentation to assess normal and cancerous tissues, infectious disease dynamics and therapeutic efficacy in real time. Some equipment items are housed in 3rd floor BSL2-level space at Biodesign (B387), to allow for study of containment level 2 agents, as well as uninfected cells and tissues. This Imaging Facility at B-CIVV includes a Core Manager who oversees the equipment usage, trains specific users, and manages the various collaborations that exploit the B-CIVV Facility Core.

Internal Collaborative Partners

Within Biodesign numerous potential internal collaborators have been launched, such as with the Center for Personalized Diagnostics (headed by Joshua LaBaer), the Center for Innovations in Medicine (headed by Stephen Johnston) and the Centers headed by Petra Fromme and Hao Yan. B-CIVV also interacts with additional centers for coordinated efforts to broaden our vision and research scope, and to foster innovative multi-disciplinary, collaborative and synergistic research approaches – for example, the BDI Centers for Bioelectronics and Biosensors; Applied Structural Discovery; Molecular Design and Biomimetics; Neurodegenerative Diseases; Sustainable Health and others. CIVV has also established connections with the following ASU groups - Mathematics and Theoretical Biology Institute; School of Biological & Health Systems Engineering; Physics; Complex Adaptive Systems Initiative (CASI); etc.  Efforts to integrate biological context and complexity into our research approaches are critical to understand the structure-function relationships and microbial adaptation strategies that drive transition between normal and disease states.  These efforts necessitate studying disease in the context of relevant microbial consortia and using predictive human surrogate in vitro and in vivo animal models that recapitulate human tissue structure and physiology. In this regard, the newly emerging Biodesign Center for Fundamental and Applied Microbiomics will likely become another logical partner for B-CIVV in the near future.

Local Collaborative Partners

B-CIVV continues to develop continuing interactions with local hospitals and research entities, such as the Mayo Clinic in Scottsdale and Phoenix Children’s Hospital, both of which have ongoing existing collaborations with B-CIVV members. Other likely partners to be developed in the future include the Translational Genomics Research Institute (TGen), the Phoenix VA Hospital, Banner Medical Center and the Barrow Neurological Institute (BNI). Another likely linkage would be with Dignity Health in Phoenix.

Biotech Partners

B-CIVV is expanding opportunities for external biotech support for both DIC and DID. For example, for DIC, the fields of oncolytic virotherapy and immunotherapy are exploding and have generated considerable interest in the biotech and pharma industries: Amgen’s T-Vec oncolytic herpesvirus received the first FDA and EU licensure for metastatic melanoma in 2015. An industrial pipeline of newly approved biological immunotherapeutics, particularly the immune checkpoint inhibitors, continues to grow rapidly. For example, Dr. Blattman’s spin-off biotech company devoted to expression tagging of co-expressed immune markers is expected to become an active partner of B-CIVV. For DID, examples of potential external corporate support include various sectors in the commercial market place that have been investing substantial funding efforts for infectious disease research. Areas of research in which multiple companies are heavily investing include novel strategies to combat antimicrobial resistance, development of probiotics to improve health and negate the risk of infectious disease, and advanced biotechnologies such as 3-D tissue engineering as predictive models for infectious disease and drug/therapeutic development. Importantly, advances with 3-D tissue engineered models and their applications to study host-microbe interactions have seen spectacular growth the past several years, including a variety of ways to enhance the physiological relevance of these models as infection and drug testing platforms to better predict in vivo outcomes. With governmental research incentives, large pharmaceutical companies have capitalized on our collective understanding of the complexity of host-pathogen interactions and have boosted antibacterial, anti-virulence, and anti-infective research and development.  A key goal will be to develop working relationships with biotech companies in these key target disease areas, especially with the assistance of the current and newly-recruited B-CIVV members and faculty.

Overall Vision

B-CIVV is poised to become a major center of scientific advances and a resource for clinical development of novel therapies against cancer, immune disorders, and infectious diseases. As well, unexpected discoveries in the mechanisms of microbial pathogenesis and host-pathogen interactions will be driven by B-CIVV scientific strengths in vaccine development, immunotherapy, virotherapy, disease dynamics, host-pathogen interactions, and next-generation therapeutics.