Overcoming key challenges in cancer immunotherapy with engineered T cells.

Abstract:

PURPOSE OF REVIEW:A number of clinical trials are currently testing chimeric antigen receptor (CAR) and T cell receptor (TCR) engineered T cells for the treatment of haematologic malignancies and selected solid tumours, and CD19-CAR-T cells have produced impressive clinical responses in B-cell malignancies. Here, we summarize the current state of the field, highlighting the key aspects required for the optimal application of CAR and TCR-engineered T cells for cancer immunotherapy. RECENT FINDINGS:Toxicities, treatment failure and disease recurrence have been observed at different rates and kinetics. Several strategies have been designed to overcome these hurdles: the identification and combination of known and new antigens, together with the combination of immunotherapeutic and classical approaches may overcome cancer immune evasion. New protocols for genetic modification and T cell culture may improve the overall fitness of cellular products and their resistance to hostile tumour immunomodulatory signals. Finally, the schedules of T cell administration and toxicity management have been adapted to improve the safety of this transformative therapeutic approach. SUMMARY:In order to develop effective adoptive T cell treatments for cancer, therapeutic optimization of engineered CAR and TCR T cells is crucial, by simultaneously focusing on intrinsic and extrinsic factors. This review focuses on the innovative approaches designed and tested to overcome the hurdles encountered so far in the clinical practice, with new excitement on novel laboratory insights and ongoing clinical investigations.

journal_name

Curr Opin Oncol

authors

Arcangeli S,Mestermann K,Weber J,Bonini C,Casucci M,Hudecek M

doi

10.1097/CCO.0000000000000664

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

398-407

issue

5

eissn

1040-8746

issn

1531-703X

pii

00001622-202009000-00003

journal_volume

32

pub_type

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