Immunotherapy in Tumors

Abstract

Background: A number of new drugs for tumor immunotherapy have been approved in the past few years. They work by activating T cells to combat tumors.

Methods: This review is based on publications on recently approved T-cell-activating drugs that were retrieved by a selective search in PubMed.

Results: Randomized, controlled trials of "checkpoint" inhibitors, i.e., inhibitory antibodies for use against tumors, have shown that the cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor ipilimumab can prolong the survival of patients with advanced melanoma by 2 to 4 months. No data on median overall survival are yet available for the two programmed-death-1 (PD-1) inhibitors pembrolizumab und nivolumab; the endpoint "tumor response" was achieved in 24% and 32% of patients receiving these drugs, respectively. Grade 3 or 4 adverse effects occurred in 50% of patients receiving ipilimumab and in 12 to 13% of those taking either of the two PD-1-inhibitors. Nivolumab prolonged the median survival of patients with metastatic non-small-cell lung cancer from 6 to 9 months. In refractory or recurrent Philadelphia-chromosome-negative pre-B acute lymphoblastic leukemia (pre-B-ALL), treatment with the bispecific antibody construct blinatumomab led to complete remission in 43% of the patients, while grade 3, 4 or 5 toxicities occurred in 83%.

Conclusion: T-cell-directed strategies have been established as a new pillar of treatment in medical oncology. As these drugs have frequent and severe adverse effects, therapeutic decision-making will have to take account not only of the predicted prolongation of survival, but also of the potential for an impaired quality of life while the patient is under treatment.

Figure

Overview of newly approved T-cell activating strategies in tumor immunotherapy. A) Antibody-based blockade of CTLA-4/CD80 and CD86 interaction B) Antibody-based blockade of PD-1/PD-L1 interaction C) T-cell activation by anti-CD3 × anti-CD19 bispecific antibody D) Treatment based on adoptive transfer of CAR-transduced T cells (not yet approved) CD, cluster of differentiation; CTLA-4, cytotoxic T-lymphocyte antigen 4; PD, programmed death; PD-L, programmed death ligand; CAR, chimeric antigen receptor