Immunotherapy and the Importance of Understanding Protein Interaction

Senior Airman Eathain Duwe, 628th Medical Group medical laboratory technician, draws blood from a patient Sept. 11, 2012, at the 628th MDG laboratory at Joint Base Charleston - Air Base, S.C. The 628th MG Laboratory conducts all clinical laboratory procedures required in support of the 628th MDG’s mission. (U.S. Air Force photo/ Airman 1st Class Chacarra Walker)

Immunotherapy is an important form of treatment for a vast number of diseases. Biomedicine is focused on the study of protein interaction networks that have provided revolutionary contributions to these therapies. While challenging, researchers continue to make immunotherapy treatments more efficient.

Immunotherapy Today

Immunotherapy induces, enhances, or suppresses an immune response to treat a specific disease. Activation immunotherapies elicit or amplify an immune response, and are mainly used to treat cancer. Suppression immunotherapies reduce or suppress a immune response. The latter is generally administered to treat allergies, prevent organ rejection, or in cases of autoimmune disease (1).

Immunotherapies involve the use of cells such as lymphocytes, macrophages, or dendritic cells, and may also utilize immunomodulators. These are active immunotherapy agents that are typically synthesized in the laboratory for a specific treatment. Some examples of immunomodulators are interleukins and cytokines. Cells and agents used in immunotherapy are extracted from our bodies, as they are already part of our immune systems. Alternately, they can be isolated from bacteria. They are replicated or recombined in-vitro and then reinjected into the patient to trigger the passive and/or adaptive immune response (2).

Cancer is a complex disease whose cells are often prone to develop resistance to therapy (3). Immunotherapy is a step away from the traditional small molecule-based cancer therapies but appears to be a viable treatment option for aggressive cancers in the near future (4). Safety, feasibility, and outcomes have already been demonstrated for tumor-associated antigen therapies, immune checkpoint inhibitors, and cell transfer immunotherapy in patients with some cancers (4).  However, tumors are very heterogeneous and are frequently the result of a combination of several diseases (5,6). A patient’s ability to generate and maintain an effective antitumor immune response poses additional challenges (3).

Interactomes and Biomedicine

An interactome is the whole set of molecular interactions in a particular cell. Researchers use different techniques and equipment to study interactomes and define protein interaction within cells. The increase in the number of interactions reported by different researches has led to the construction of large and complex databases of experimentally determined protein-protein interaction networks (7). The extensive mapping of interactomes provides insight that aids in the development of more effective immunotherapies, and can allow researchers to predict a patient’s response to them.

In recent years, there has been a decline in the productivity of the pharmacological industry that may be due to the underestimation of the complexity of cells, organisms, and human disease (8).  Consequently, there is an interest for laboratories to understand the whole dynamic of protein interaction networks in order to reverse this trend. Interactomes reveal the immune evasion strategies of some tumors, allowing doctors the possibility to treat cancers in the first stages and improve prognosis.

After decades of research, cancer immunotherapy has finally found its place. Within the last six years, the first therapeutic cancer vaccines, monoclonal antibodies targeting immune checkpoints, and oncolytic virus encoding GM-CSF have been approved (9). Researchers are concentrating on developing effective therapies for aggressive cancers with the goal of establishing better immunotherapy results similar to those currently seen in the treatment of some allergies and autoimmune diseases.

References:

1. Prendergast G, Jaffee E. Cancer Immunotherapy: Immune Suppression and Tumor Growth. August 2018. Academic Press, Ed.

2. Li K, Li CK, Chuen CK, Tsang KS, Fok TF, James AE, Lee SM, Shing MM, Chik KW, Yuen PM. Preclinical ex vivo expansion of G-CSF-mobilized peripheral blood stem cells: effects of serum-free media, cytokine combinations and chemotherapy. (2005) Eur. J. Haematology. 74 (2): 128–35. doi:10.1111/j.1600-0609.2004.00343.x. PMID 15654904

3. Fox B. Defining the critical hurdles in cancer immunotherapy. J Transl Med. 2011; 9: 214. Published online 2011 Dec 14. doi:  10.1186/1479-5876-9-214.

4. Tsuchiya N, Sawada Y, Endo I, Uemura Y, Nakatsura T. Potentiality of immunotherapy against hepatocellular carcinoma. World J Gastroenterology. 2015 Sep 28; 21(36): 10314–10326. Published online 2015 Sep  28. doi:  10.3748/wjg.v21.i36.10314

5. Visvader JE. Cells of origin in cancer. Nature. pp. 314–22.

6. Damia G, D’Incalci M. Genetic instability influences drug response in cancer cells. Curr Drug Targets. pp. 1317–24.

7. Ghadie M, Lambourne L, Vidal M, Xia Y. Domain-based prediction of the human isoform interactome provides insights into the functional impact of alternative splicing. PLoS Comput Biol. 2017 Aug; 13(8): e1005717.

Published online 2017 Aug 28. doi:  10.1371/journal.pcbi.1005717

8. Lowe JA, Jones P, Wilson DM. Network biology as a new approach to drug discovery. Curr Opin Drug Discov Devel. 2010;13:524–526.

9. Smith S, Zaharoff D. Future directions in bladder cancer immunotherapy: towards adaptive immunity. Immunotherapy. 2016 Mar; 8(3): 351–365. Published online 2016 Feb 10. doi:  10.2217/imt.15.122

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