Exploiting Radiation Induction of Antigens in Cancer: Targeted Drug Delivery

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Mar 25

PMID 35328459

Authors

Vaishali Kapoor

Abhay K Singh

Calvin D Lewis

Sapna Deore

Dennis E Hallahan

Affiliations

Soon will be listed here.

Abstract

Therapeutic antibodies used to treat cancer are effective in patients with advanced-stage disease. For example, antibodies that activate T-lymphocytes improve survival in many cancer subtypes. In addition, antibody-drug conjugates effectively target cytotoxic agents that are specific to cancer. This review discusses radiation-inducible antigens, which are stress-regulated proteins that are over-expressed in cancer. These inducible cell surface proteins become accessible to antibody binding during the cellular response to genotoxic stress. The lead antigens are induced in all histologic subtypes and nearly all advanced-stage cancers, but show little to no expression in normal tissues. Inducible antigens are exploited by using therapeutic antibodies that bind specifically to these stress-regulated proteins. Antibodies that bind to the inducible antigens GRP78 and TIP1 enhance the efficacy of radiotherapy in preclinical cancer models. The conjugation of cytotoxic drugs to the antibodies further improves cancer response. This review focuses on the use of radiotherapy to control the cancer-specific binding of therapeutic antibodies and antibody-drug conjugates.

Citing Articles

Proton radiation boosts the efficacy of mesothelin-targeting chimeric antigen receptor T cell therapy in pancreatic cancer.

Amit U, Uslu U, Verginadis I, Kim M, Oliaei Motlagh S, Diffenderfer E Proc Natl Acad Sci U S A. 2024; 121(31):e2403002121.

PMID: 39047033 PMC: 11294999. DOI: 10.1073/pnas.2403002121.

Development of a [89Zr]Zr-labeled Human Antibody using a Novel Phage-displayed Human scFv Library.

Singh A, Lewis C, Boas C, Diebolder P, Jethva P, Rhee A Clin Cancer Res. 2024; 30(7):1293-1306.

PMID: 38277241 PMC: 10984770. DOI: 10.1158/1078-0432.CCR-23-3647.

References

Lin A, Campian J, Hui C, Rudra S, Rao Y, Thotala D . Impact of concurrent versus adjuvant chemotherapy on the severity and duration of lymphopenia in glioma patients treated with radiation therapy. J Neurooncol. 2017; 136(2):403-411. DOI: 10.1007/s11060-017-2668-5. View

Han Z, Fu A, Wang H, Diaz R, Geng L, Onishko H . Noninvasive assessment of cancer response to therapy. Nat Med. 2008; 14(3):343-9. DOI: 10.1038/nm1691. View

Alfaleh M, Alsaab H, Mahmoud A, Alkayyal A, Jones M, Mahler S . Phage Display Derived Monoclonal Antibodies: From Bench to Bedside. Front Immunol. 2020; 11:1986. PMC: 7485114. DOI: 10.3389/fimmu.2020.01986. View

Dadey D, Kapoor V, Hoye K, Khudanyan A, Collins A, Thotala D . Antibody Targeting GRP78 Enhances the Efficacy of Radiation Therapy in Human Glioblastoma and Non-Small Cell Lung Cancer Cell Lines and Tumor Models. Clin Cancer Res. 2016; 23(10):2556-2564. DOI: 10.1158/1078-0432.CCR-16-1935. View

Barth R, Mi P, Yang W . Boron delivery agents for neutron capture therapy of cancer. Cancer Commun (Lond). 2018; 38(1):35. PMC: 6006782. DOI: 10.1186/s40880-018-0299-7. View

Reardon D, Lassman A, van den Bent M, Kumthekar P, Merrell R, Scott A . Efficacy and safety results of ABT-414 in combination with radiation and temozolomide in newly diagnosed glioblastoma. Neuro Oncol. 2017; 19(7):965-975. PMC: 5570193. DOI: 10.1093/neuonc/now257. View

Bensch F, van der Veen E, Lub-de Hooge M, Jorritsma-Smit A, Boellaard R, Kok I . Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade in cancer. Nat Med. 2018; 24(12):1852-1858. DOI: 10.1038/s41591-018-0255-8. View

Coats S, Williams M, Kebble B, Dixit R, Tseng L, Yao N . Antibody-Drug Conjugates: Future Directions in Clinical and Translational Strategies to Improve the Therapeutic Index. Clin Cancer Res. 2019; 25(18):5441-5448. DOI: 10.1158/1078-0432.CCR-19-0272. View

Hallahan D, Geng L, Qu S, Scarfone C, Giorgio T, Donnelly E . Integrin-mediated targeting of drug delivery to irradiated tumor blood vessels. Cancer Cell. 2003; 3(1):63-74. DOI: 10.1016/s1535-6108(02)00238-6. View

10.

Dadey D, Kapoor V, Khudanyan A, Thotala D, Hallahan D . PERK Regulates Glioblastoma Sensitivity to ER Stress Although Promoting Radiation Resistance. Mol Cancer Res. 2018; 16(10):1447-1453. DOI: 10.1158/1541-7786.MCR-18-0224. View

11.

Patel D, Bassi R, Hooper A, Prewett M, Hicklin D, Kang X . Anti-epidermal growth factor receptor monoclonal antibody cetuximab inhibits EGFR/HER-2 heterodimerization and activation. Int J Oncol. 2008; 34(1):25-32. View

12.

Lyon R . Drawing lessons from the clinical development of antibody-drug conjugates. Drug Discov Today Technol. 2018; 30:105-109. DOI: 10.1016/j.ddtec.2018.10.001. View

13.

Cirrone G, Manti L, Margarone D, Petringa G, Giuffrida L, Minopoli A . First experimental proof of Proton Boron Capture Therapy (PBCT) to enhance protontherapy effectiveness. Sci Rep. 2018; 8(1):1141. PMC: 5773549. DOI: 10.1038/s41598-018-19258-5. View

14.

Jaboin J, Han Z, Hallahan D . Using in vivo biopanning for the development of radiation-guided drug delivery systems. Methods Mol Biol. 2009; 542:285-300. DOI: 10.1007/978-1-59745-561-9_15. View

15.

Hassan R, Williams-Gould J, Steinberg S, Liewehr D, Yokokawa J, Tsang K . Tumor-directed radiation and the immunotoxin SS1P in the treatment of mesothelin-expressing tumor xenografts. Clin Cancer Res. 2006; 12(16):4983-8. DOI: 10.1158/1078-0432.CCR-06-0441. View

16.

Juan A, Cimas F, Bravo I, Pandiella A, Ocana A, Alonso-Moreno C . Antibody Conjugation of Nanoparticles as Therapeutics for Breast Cancer Treatment. Int J Mol Sci. 2020; 21(17). PMC: 7504566. DOI: 10.3390/ijms21176018. View

17.

Kleinberg L, Sloan L, Grossman S, Lim M . Radiotherapy, Lymphopenia, and Host Immune Capacity in Glioblastoma: A Potentially Actionable Toxicity Associated With Reduced Efficacy of Radiotherapy. Neurosurgery. 2019; 85(4):441-453. DOI: 10.1093/neuros/nyz198. View

18.

Beck A, Goetsch L, Dumontet C, Corvaia N . Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov. 2017; 16(5):315-337. DOI: 10.1038/nrd.2016.268. View

19.

Gray J, Villegas A, Daniel D, Vicente D, Murakami S, Hui R . Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC-Update from PACIFIC. J Thorac Oncol. 2019; 15(2):288-293. PMC: 7244187. DOI: 10.1016/j.jtho.2019.10.002. View

20.

Bonner J, Harari P, Giralt J, Cohen R, Jones C, Sur R . Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2009; 11(1):21-8. DOI: 10.1016/S1470-2045(09)70311-0. View