More Haste, Less Speed: Could Public–Private Partnerships Advance Cellular Immunotherapies?

Cellular immunotherapies promise to transform cancer care. However, they must overcome serious challenges, including: (1) the need to identify and characterize novel cancer antigens to expand the range of therapeutic targets; (2) the need to develop strategies to minimize serious adverse events, such as cytokine release syndrome and treatment-related toxicities; and (3) the need to develop efficient production/manufacturing processes to reduce costs. Here, we discuss whether these challenges might better be addressed through forms of public–private research collaborations, including public–private partnerships (PPPs), or whether these challenges are best addressed by way of standard market transactions. We reviewed 14 public–private relationships and 25 underlying agreements for the clinical development of cancer cellular immunotherapies in the US. Most were based on bilateral research agreements and pure market transactions in the form of service contracts and technology licenses, which is representative of the commercialization focus of the field. We make the strategic case that multiparty PPPs may better advance cancer antigen discovery and characterization and improved cell processing/manufacturing and related activities. In the rush toward the competitive end of the translational continuum for cancer cellular immunotherapy and the attendant focus on commercialization, many gaps have appeared in our understanding of cellular biology, immunology, and bioengineering. We conclude that the model of bilateral agreements between leading research institutions and the private sector may be inadequate to efficiently harness the interdisciplinary skills and knowledge of the public and private sectors to bring these promising therapies to the clinic for the benefit of cancer patients

Quantitative analysis of the extracellular glutamate concentration of the nucleus accumbens

Intracerebral microdialysis was used to sample neurotransmitters from the extracellular fluid of the nucleus accumbens (NAS). Sample concentrations of dopamine and glutamate were assayed using high performance liquid chromatography followed by electrochemical detection. Sample glutamate concentrations decreased and then increased during the first ten to twelve hours following probe implantation. After stabilization sample glutamate and dopamine concentrations were estimated at a range of flow rates (0.25 $\mu$l/m, 0.5 $\mu$l/m, 1.0 $\mu$l/m, 2.0 $\mu$l/m); dopamine and glutamate concentrations varied inversely with the rate of perfusion. Estimates of the normal NAS extracellular glutamate and dopamine concentrations could not be obtained from these data using the "extrapolation to zero flow" method because there was no evidence of asymptotic yield within the range of flow rates that could be tested. An estimate of the normal NAS extracellular glutamate concentration (4.0 $\pm$ 0.8) was obtained using the no-net-flux method. The no-net-flux estimate was not significantly affected by an increase in the local depletion of dopamine and other small molecules caused by doubling the perfusate flow rate. The estimated extracellular glutamate concentration was 3.8 $\pm$ 0.8 $\mu$M at a flow rate of 0.5 $\mu$l/m and 4.25 $\pm$ 0.9 $\mu$M at a flow rate of 1.0 $\mu$l/min. These concentrations are not significantly different, suggesting that this increase in local depletion did not influence the activity of glutamate releasing cells in the tissue adjacent to the probe. Changes in dialysis sample dopamine concentration were determined during the extraction of NAS glutamate or the delivery of glutamate to the NAS. No significant changes in the sample dopamine concentration were associated with the perfusion of a range of glutamate concentrations surrounding the estimated NAS extracellular glutamate concentration