Although targeted therapy is generally applied to the use of small molecules that target specific genes or proteins of diseased cells, it is now possible to target immune cells against specific diseases through genetic modification. This provides desired antigen-specificity to powerful cell-mediated cytotoxicity effects. Small studies show impressive results both in blood cancers and viral infections refractory to other therapies. Toxicity and efficacy vary with the diseases being treated and the cell products used. In addition, new approaches to genetically-modify blood stem cells are being evaluated to prevent viral infection, i.e. HIV, or correct hematopoietic stem cell derivatives, and these approaches could cure diseases for which good treatments are not currently available.

Both preclinical and clinical studies are needed to identify optimal cell types and gene constructs, use of “universal” donors, and magnitude and durability of clinical effects. Effective infrastructure to provide the right cells at the right time is necessary to test clinical efficacy.

Elucidation of molecular and cellular pathways driving and sustaining exacerbations in chronic lung diseases. Specifically, (1) discover what perturbs antecedent conditions precipitating mal(adaptive) compensatory mechanisms leading to pulmonary exacerbation including impact of heterogeneous resilience and concomitant chronic diseases and (2) clarify response heterogeneity of longitudinal molecular and cellular signature during treatment and recovery.

Longitudinal pulmonary exacerbation research nested with clinical care can be initiated within 1-2 years. As part of clinical care leveraging digital education/data (electronic health/medical records and attendant meaningful use requirements), an N-of-one research design could become self-sustaining within health care systems.
Pulmonary exacerbations exhibit multiple pathogenic pathways various concurrent pathophysiological pathways, and diverse clinical manifestations. Prevention and treatment of pulmonary exacerbations is hampered by this complex biology that is dynamic and appears to vary during the course of exacerbations. Progress toward precision medicine for exacerbations may require organization of a new taxonomy for disease, which reflects a set of clinically meaningful and exploitable similarities and differences between disease traits (exacerbation polypathomics).

As the body of evidence continues to grow on the potential applications for advanced immunotherapies, next-generation research must focus on addressing the possible curative effects that checkpoint blockades or adoptive CAR T-cell strategies can have for blood diseases including hematologic cancers. This will require specific research programs to fully understand the optimal role for these therapies within the continuum of care. To optimize these strategies for treatment of hematologic diseases, studies are needed to decipher specific hematologic diseases and circumstances under which these checkpoint blockers and CAR T-cell therapies may be employed as frontline approaches. Furthermore, while the optimal approach for these therapies is unclear, advanced studies are needed to elucidate the potential benefit in combining these promising approaches and whether patients can be better identified a priori for these therapies.

Addressing this line of research could define biomarkers and pathways useful for prediction of how human response to an external stimulus of varied nature (i.e. microorganism, chemical, physical) could lead to specific outcomes in relationship to the duration of the exposure and the genetic makeup of the individual exposed. Identification of early signals and the pathways involved could lead to novel preventative or therapeutic approaches.

Methods for systems biology approaches to address complex pathobiological iterations are ready to be exploited to answer these questions.
Great progress has been made in the clarification of basic mechanisms of molecular and cellular response to environmental stimuli, in cross-sectional analyses. The continuum of the response in relationship to the genetic background of individuals responding with a homeostatic or pathological long-term outcome is missing from these data.

Development of methods for near term or long term surveillance after transplant can help detect the rejection and thus improve patient survival

The fast growth in the imaging technologies and molecular and cellular imaging technologies are gaining foot in cardiovascular sciences and should be feasible within a decade
The current surveillance to detect transplant rejection requires repeated testing with endo myocardial biopsy and catheter angiography. Both technologies are highly invasive and very expensive. Post-transplant surveillance is focused on the cellular rejection in the near term after transplant and cardiac allograft vasculopathy in the long term.

Physiologically relevant in vitro environments could potentially impact research on every tissue type, disease, and intervention, including transfusion-based treatments. Basic research, drug-testing, and translational medicine would all be fundamentally altered. Individualized medicine, cellular therapies, and regenerative medicine could all benefit from in vitro conditions that best support the care of the patient's cells and guide those cells in the direction needed for effective treatment.

Research and Industry are in the early stages of developing the techniques and know-how needed to address the technical challenges in establishing human-relevant in vitro environments. We already have the technology to control in vitro oxygen and other critical gas components. Mimicking cell-cell interactions and variable cell states such as states of differentiation or stress are areas under active research. Computational and analytical techniques are being developed that can gain insight from large data sets. More of a challenge may be assessing distant effects like metabolism of drugs by the liver or potential drug and cellular interactions with the external environment. However, making a human-predictive in vitro environment affordable is the challenge that could define success or failure of any particular approach. It is feasible within the next ten years to have truly predictive in vitro environments for drug cellular therapy development.

Recent analyses suggest that the pool of patients who could benefit from stem cell-based therapies could be as high as 100 million. The actual number of patients receiving stem cell therapies is actually substantially lower than that (< 500,000). it has been postulated that one reason for the gap between the potential patient pool and the actual patient pool has resulted from poor methods of preservation. The failure of recent clinical trials using mesenchymal stem cells support that hypothesis.

When developing a cellular therapy, supply chain issues (e.g. preservation) is frequently ignored until the failure of a clinical trial. If preservation issues are addressed concurrently with the development of a cellular therapy, the feasibility of addressing the issue is high.

There are two critical challenges to addressing this critical challenge: (1) preservation studies are not considered 'sexy' and therefore score poorly in conventional study sections; and (2) organizations developing a cellular therapy do not have a team member with expertise in preservation.

Need more opportunities to put forth innovative diagnostic and therapeutic solutions than currently vetted through the CTSC process.
We have developed the Artery-on-a-chip (A-chip), currently in a research tool format, which accurately measures the extent of inflammatory monocyte activation in a whole blood sample by shearing it along a molecular sensor and enumerating monocyte capture.