The Global Landscape of Cellular Immunotherapy Clinical Trials

Z. Breckenridge, K. Bonter, K. Lea, T. Bubela

Background: Cancer remains one of the leading causes of morbidity and mortality worldwide, with the number of new cases expected to rise by seventy percent over the next two decades. Conventional therapies are highly invasive, have significant adverse effects, and are generally not curative. Cellular immunotherapy (CI) is far less invasive, and shows curative potential for patients with both established tumors and hematological malignancy.

Objective: We describe the global landscape of CI trials derived from clinical trial registrations and publications. We analyze trends in CI to predict future development patterns, expected efficacy, business models, manufacturing requirements, clinical trial designs, and clinical applications.

Methods: We sampled trials registered between 1992 and September 2014 from the four largest clinical trial registries worldwide. In consultation with CI experts, we developed a search algorithm which yielded 16, 593 non-observational and unique trials. We applied inclusion/exclusion criteria, resulting in a dataset of 1337 CI trial registrations. We then manually reviewed trial registrations and linked publications for forty-five informational fields, including cell type, ex vivo manipulations, manufacturing processes, dose, co-interventions, and industry affiliation.

Results: Of the 1337 trials in our dataset, 512 trials were completed between 1992 and 2012, while 532 trials are expected to be completed between 2013 and 2016. The number of trials employing active immunization approaches (i.e. dendritic cell vaccines) was superseded in 2012 by trials employing passive approaches (i.e. ex vivo modified lymphocytes). Trends indicate that CI interventions are increasing in specificity in terms of antigenic target, and complexity in ex vivo manipulation.

Significance: Clinical translation of CI is progressing rapidly. While most trials are still early-stage and sponsored by academic centres, industry sponsorship and collaboration is increasing. Clinical trial registries are a rich source of data on manufacturing and clinical adoption models which, in turn, will inform business models for the nascent field of CI. The next steps will be to employ these data in cost effectiveness models to ensure CI is developed in a manner that health systems and patients can afford.