Evolving synergistic combinations of targeted immunotherapies to combat cancer

Abstract

Immunotherapy has now been clinically validated as an effective treatment for many cancers. There is tremendous potential for synergistic combinations of immunotherapy agents and for combining immunotherapy agents with conventional cancer treatments. Clinical trials combining blockade of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) may serve as a paradigm to guide future approaches to immuno-oncology combination therapy. In this Review, we discuss progress in the synergistic design of immune-targeting combination therapies and highlight the challenges involved in tailoring such strategies to provide maximal benefit to patients.

Is autoimmunity the Achilles' heel of cancer immunotherapy?

“…Indeed, the emerging standard of care for patients with many forms of disseminated cancer is therapy with a checkpoint antagonist. Moreover, for patients in clinical trials, the trend is to combine one or several of the increasing 'toolbox of therapies,' including vaccines, CAR T cells, oncolytic viruses, radiation, chemotherapy, and targeted therapies, with a checkpoint blocker 65 .…”

Oncostatin M treatment increases the responsiveness toward cisplatin‑based chemoradiotherapy in cervical cancer cells in a STAT3‑dependent manner

“…Targeted therapy strategies include several antibodies or inhibitors to block essential biochemical pathways required for tumor growth and survival, like EGFR, VEGF, BRAF or HER2 (21). Blockage of the inhibitory proteins CTLA-4, PD-1 or the ligand PD1-L with specific antibodies, checkpoint inhibitors (22), resulted in clinical benefit in several tumor types (23)(24)(25).…”

Management of Italian Patients With Advanced Non–Small-Cell Lung Cancer After Second-Line Treatment: Results of the Longitudinal Phase of the LIFE Observational Study

“…As a homologue to CD4, LAG3 expressed on effector CD4 þ T cells is deemed as a negative modulator tending to have interaction with major histocompatibility complex (MHC) II molecules. 35 LAG3 is also required for T reg to maintain the suppressive function. Moreover, galectin-3 and L-selectin have been discovered as the ligands for LAG3 expressed on CD8 þ T cells to inhibit the antitumor response, 36,37 or other possible ligands, not defined.…”