Recent advances in T-cell immunotherapy for haematological malignancies

Abstract

In vitro discoveries have paved the way for bench-to-bedside translation in adoptive T cell immunotherapy, resulting in remarkable clinical responses in a variety of haematological malignancies. Adoptively transferred T cells genetically modified to express CD19 CARs have shown great promise, although many unanswered questions regarding how to optimize T-cell therapies for both safety and efficacy remain. Similarly, T cells that recognize viral or tumour antigens though their native receptors have produced encouraging clinical responses. Honing manufacturing processes will increase the availability of T-cell products, while combining T-cell therapies has the ability to increase complete response rates. Lastly, innovative mechanisms to control these therapies may improve safety profiles while genome editing offers the prospect of modulating T-cell function. This review will focus on recent advances in T-cell immunotherapy, highlighting both clinical and pre-clinical advances, as well as exploring what the future holds.

Keywords: T cells; immunotherapy; lymphoma.

Figure 1. Mechanisms of T-cell mediated immunotherapy

Targeting tumours using native TCR: a). Recognition of TAAs (tumour-associated antigens) via native TCR (T cell receptor) b) Virus-specific T cells (VSTs) are able to recognize virus-associated tumour antigens via native TCR. Genetic modification of T cells c). Transgenic or modified TCRs recognizing tumour antigens. d). Chimeric antigen Receptors (CARs) targeting TAAs Combination Approaches: e) Immune checkpoint blockade/ small molecule inhibitors in T cells recognizing tumour through their TCR to enhance the adoptive immunotherapy. f) Immune checkpoint blockade/ small molecule inhibitors in genetically engineered CAR T cells.