Advances in cancer immunotherapy 2019 – latest trends

Abstract

Immunotherapy has become an established pillar of cancer treatment improving the prognosis of many patients with a broad variety of hematological and solid malignancies. The two main drivers behind this success are checkpoint inhibitors (CPIs) and chimeric antigen receptor (CAR) T cells. This review summarizes seminal findings from clinical and translational studies recently presented or published at important meetings or in top-tier journals, respectively. For checkpoint blockade, current studies focus on combinational approaches, perioperative use, new tumor entities, response prediction, toxicity management and use in special patient populations. Regarding cellular immunotherapy, recent studies confirmed safety and efficacy of CAR T cells in larger cohorts of patients with acute lymphoblastic leukemia or diffuse large B cell lymphoma. Different strategies to translate the striking success of CAR T cells in B cell malignancies to other hematological and solid cancer types are currently under clinical investigation. Regarding the regional distribution of registered clinical immunotherapy trials a shift from PD-1 / PD-L1 trials (mainly performed in the US and Europe) to CAR T cell trials (majority of trials performed in the US and China) can be noted.

TIGIT as an emerging immune checkpoint

“…Monoclonal antibodies (mAbs) targeting the inhibitory receptors cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4) and programmed cell death 1 (PD‐1) have shown clinical efficacy and durable responses in more than 15 types of human malignancy . The importance of immune checkpoint blockade (ICB) in revolutionizing modern cancer therapy has been acknowledged by the Nobel Prize in Physiology or Medicine 2018 being awarded to James P. Allison and Tasuko Honjo for their discovery of cancer therapy by inhibition of CTLA‐4 and PD‐1, respectively .…”

Identification of Novel Small-Molecule Kinase Modulators for the Treatment of Neuroblastoma

“…Immunotherapy is another therapeutic approach that has resulted in successful outcomes in other cancers. In recent years, anti-PD-1/PD-L1 or anti-CTLA-4 antibodies have revolutionized cancer therapy for many tumors, from melanoma to lung cancer [26]-but this fruitful outcome has not yet reached neuroblastoma patients. Only one anti-disialoganglioside antibody (dinutuximab) has come on the market for neuroblastoma patients, and although this monoclonal antibody has improved the outcome in high-risk patients, it is only prescribed to patients who have successfully completed both induction and consolidation therapies [27].…”

3D Immunocompetent Organ‐on‐a‐Chip Models

“…In recent years, cancer immunotherapy has become a potential approach that harnesses patient's immune system to recognize and selectively ablate cancer cells. [ 142–144 ] For cancer immunotherapy, a variety of strategies such as modulation of the immune system, administration of the exogenous cytokines (IL‐2 and IFN‐α), engineered T cells (chimeric antigen receptor‐modified T cells (CAR‐T) and TCR‐T cells), and immune checkpoint blockade with antibodies targeting the immune check point inhibitors (programmed cell death protein 1 (PD‐1)/PD‐1 ligand (PD‐L1) and cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4)), have been used to activate the immune system and to fight cancer. [ 145–150 ] Other immunotherapies include cell‐based immunotherapy whereby naïve or engineered immune cells, such as cytotoxic CD8 + T cells or NK cells, are administrated into the bloodstream to destroy the tumor cells by secreting TNF‐α, perforins, or apoptosis‐inducing proteins such as TNF‐related apoptosis‐inducing ligand (TRAIL) and granzymes.…”