The Role of Checkpoint Inhibitors and Cytokines in Adoptive Cell-Based Cancer Immunotherapy with Genetically Modified T Cells

  title={The Role of Checkpoint Inhibitors and Cytokines in Adoptive Cell-Based Cancer Immunotherapy with Genetically Modified T Cells},
  author={Pavel M. Gershovich and A. V. Karabelskii and Andrey Borisovich Ulitin and R. A. Ivanov},
  journal={Biochemistry (Moscow)},
This review focuses on the structure and molecular action mechanisms of chimeric antigen receptors (CARs) and major aspects of the manufacturing and clinical application of products for the CAR-T (CAR-modified T lymphocyte) therapy of hematological and solid tumors with special emphasis on the strategies for combined use of CAR-T therapy with immuno-oncological monoclonal antibodies (checkpoint inhibitors) and cytokines to boost survival, persistence, and anti-tumor efficacy of CAR-T therapy… 
2 Citations
Thematic Issue: Immuno-Oncology and Immunotherapy
The articles included in this thematic issue highlight the topical aspects of cancer immunotherapy by presenting different viewpoints of scientists, physicians, and drug developers.
Immunotherapy with immune checkpoint inhibitors in colorectal cancer: what is the future beyond deficient mismatch-repair tumours?
The current status of ICIs, the role of biomarkers to predict response to immunotherapy, and the approaches being explored to render pMMR/MSS CRC more immunogenic through the use of combined therapies are discussed.


Cancer immunotherapies targeting the PD-1 signaling pathway
The development of PD-1-blockade immunotherapy and current issues in its clinical use are summarized.
Anti-PD-1 Antibody Therapy Potently Enhances the Eradication of Established Tumors By Gene-Modified T Cells
This study shows that specifically blocking PD-1 immunosuppression can potently enhance CAR T-cell therapy that has significant implications for potentially improving therapeutic outcomes of this approach in patients with cancer.
CAR T Cells in Solid Tumors: Blueprints for Building Effective Therapies
A novel three-pronged approach for enhancing the efficacy of CAR T cells is presented whereby a single infusion product can synergize the power of an optimal CAR construct, a highly potent T cell subset, and rejuvenate the endogenous immune response to conquer therapeutically-resistant solid tumors.
Interleukin 15 as a promising candidate for tumor immunotherapy.
Chimeric antigen receptor therapy for cancer.
This new form of targeted immunotherapy merges the exquisite targeting specificity of monoclonal antibodies with the potent cytotoxicity and long-term persistence provided by cytotoxic T cells to create an entirely new arena for targeted therapy of cancer.
Enhanced Cancer Immunotherapy by Chimeric Antigen Receptor–Modified T Cells Engineered to Secrete Checkpoint Inhibitors
This study demonstrated that the secretion of anti–PD-1 enhanced the antitumor activity of CAR T cells and prolonged overall survival and presented an important and novel strategy that enables CAR T Cells to achieve better antitumors immunity, especially in the treatment of solid tumors.
Cellular Immune Responses and Immune Escape Mechanisms in Breast Cancer: Determinants of Immunotherapy
If the immune balance of disseminated BC cell dormancy (equilibrium phase) is lost, distant metastatic relapse may occur and the mechanisms of immune evasion leading to tumor progression are dissected.
A Phase I Study on Adoptive Immunotherapy Using Gene-Modified T Cells for Ovarian Cancer
Large numbers of gene-modified tumor-reactive T cells can be safely given to patients, but these cells do not persist in large numbers long term, and future studies need to employ strategies to extend T cell persistence.
CARs: Synthetic Immunoreceptors for Cancer Therapy and Beyond.