Choice of activation protocol impacts the yield and quality of CAR T cell product, particularly with older individuals.

Objectives: In clinical chimeric antigen receptor (CAR) T cell therapy, one of the strongest correlates of favorable patient responses is lower levels of differentiation in T cells from the peripheral blood mononuclear cell (PBMC) starting material or the CAR T cell product. T cells from older patients are inherently more differentiated, but we hypothesised that specific activation protocols could be used to limit CAR T cell differentiation during manufacturing, particularly in older patients.

Methods: We used PBMCs from young (20-30 years old) and older (60+ years old) healthy donors to generate CAR T cells using two activation protocols: soluble anti-(α) CD3 monoclonal antibody (mAb) immune complexes of αCD3 and αCD28 mAbs.

T Cell Fitness and Autologous CAR T Cell Therapy in Haematologic Malignancy.

A range of emerging therapeutic approaches for the treatment of cancer aim to induce or augment endogenous T cell responses. Chimeric antigen receptor (CAR) T cell therapy (CTT) is one such approach that utilises the patient's own T cells, engineered to target cell surface antigens, to eliminate haematological malignancies. Despite mediating high rates of responses in some clinical trials, this approach can be limited by dysfunctional T cells if they are present at high frequencies either in the starting material from the patient or the CAR T cell product.

The Gastrointestinal Helminth Suppresses Inflammation in a Model of Contact Hypersensitivity.

Helminths regulate host immune responses to ensure their own long-term survival. Numerous studies have demonstrated that these helminth-induced regulatory mechanisms can also limit host inflammatory responses in several disease models. We used the infection model (also known as or in the literature) to test whether such immune regulation affects skin inflammatory responses induced by the model contact sensitiser dibutyl phthalate fluorescein isothiocynate (DBP-FITC).