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

Blasts in context:the impact of the immune environment on acute myeloid leukemia prognosis and treatment

Acute myeloid leukemia (AML) is a cancer that originates from the bone marrow (BM). Under physiological conditions, the bone marrow supports the homeostasis of immune cells and hosts memory lymphoid cells. In this review, we summarize our present understanding of the role of the immune microenvironment on healthy bone marrow and on the development of AML, with a focus on T cells and other lymphoid cells. The types and function of different immune cells involved in the AML microenvironment as well as their putative role in the onset of disease and response to treatment are presented. We also describe how the immune context predicts the response to immunotherapy in AML and how these therapies modulate the immune status of the bone marrow. Finally, we focus on allogeneic stem cell transplantation and summarize the current understanding of the immune environment in the post-transplant bone marrow, the factors associated with immune escape and relevant strategies to prevent and treat relapse.</p

How Can We Raise Awareness of Physician’s Needs in Order to Increase Adherence to Management and Leadership Training?

Due to the increasing complexity of medical education and practice, the training of healthcare professionals for leadership and management roles and responsibilities has become increasingly important. But gaps in physician leadership and management skills have been identified across a broad range of organizational and geographic settings. Many clinicians are inadequately prepared to meet their day-to-day clinical leadership responsibilities. Simultaneously, physicians’ leadership and management skills play a central role and yield superior outcomes for patients and health care delivery organizations. Currently, there is a tremendous variability in the amount of time, structure and resources dedicated to leadership/management training for physicians. Physicians who have completed such trainings seem to be pleased with the outcome. However, only a limited number of physicians enroll in these types of trainings. Several reasons can explain this fact, but it seems crucial to investigate what could increase the involvement of medical leaders and managers in these training programs. This paper offers a framework for addressing the barriers to training commitment and for designing initial training interventions for physicians. This framework is rooted in two well-known theoretical models used in social sciences. It aims to promote self-assessed knowledge and expertise amongst physicians about to embrace leader/manager careers. By developing the ability to explore and be curious about one’s own experience and actions, physicians may suddenly open up the possibilities of purposeful learning. The process we describe in this paper may be an essential step in fostering the involvement of physicians in leadership and management training processes. And this is essential to contribute to the advancement of medical discipline

Two types of human TCR differentially regulate reactivity to self and non-self antigens.

peer reviewedBased on analyses of TCR sequences from over 1,000 individuals, we report that the TCR repertoire is composed of two ontogenically and functionally distinct types of TCRs. Their production is regulated by variations in thymic output and terminal deoxynucleotidyl transferase (TDT) activity. Neonatal TCRs derived from TDT-negative progenitors persist throughout life, are highly shared among subjects, and are reported as disease-associated. Thus, 10%-30% of most frequent cord blood TCRs are associated with common pathogens and autoantigens. TDT-dependent TCRs present distinct structural features and are less shared among subjects. TDT-dependent TCRs are produced in maximal numbers during infancy when thymic output and TDT activity reach a summit, are more abundant in subjects with AIRE mutations, and seem to play a dominant role in graft-versus-host disease. Factors decreasing thymic output (age, male sex) negatively impact TCR diversity. Males compensate for their lower repertoire diversity via hyperexpansion of selected TCR clonotypes