What will (and should) be improved in CAR immunotherapy?

Chimeric antigen receptor (CAR) is probably one of the most successful proposals for cancer treatment, especially hematological diseases for which several Advanced Therapies Medicinal Products (ATMP) have been approved worldwide by drug agencies. But, despite this unprecedented success in the oncology and cell/gene therapy fields, there are a lot of aspects that could (and should) be improved in the multiple aspects that involve this complex therapy: from the design of the chimeric molecule to the clinical protocols of use of the engineered T-cells, including even the regulatory rules that they are currently restricting the development of these hopeful therapies. In this chapter, we will try to summarize the main aspects that can (and probably should) be improved for the expansion of immunotherapy with CAR proposals beyond onco-hematology.

Manufacturing and Management of CAR T-Cell Therapy in "COVID-19's Time": Central Versus Point of Care Proposals.

The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has generated a significant repercussion on the administration of adoptive cell therapies, including chimeric antigen receptor (CAR) T-cells. The closing of borders, the reduction of people transit and the confinement of the population has affected the supply chains of these life-saving medical products. The aim of this mini-review is to focus on how the COVID-19 pandemic has affected CAR T-cell therapy and taking into consideration the differences between the large-scale centralized productions for the pharmaceutical industry versus product manufacturing in the academic/hospital environment. We also review different aspects of CAR T-cell therapy and our managerial experience of patient selection, resource prioritization and some practical aspects to consider for safe administration. Although hospitals have been forced to change their usual workflows to cope with the saturation of health services by hospitalized patients, we recommend centers to continue offering this potentially curative treatment for patients with relapsed/refractory hematologic malignancies. Consequently, we propose appropriate selection criteria, early intervention to attenuate neurotoxicity or cytokine release syndrome with tocilizumab and prophylactic/preventive strategies to prevent infection. These considerations may apply to other emerging adoptive cell treatments and the corresponding manufacturing processes.