Release Date: 2024-06-05

Immunotherapy in Cancer Treatment: Current and Future Directions

Duriye Ozturk (Author)

Release Date: 2024-06-05

This section presents a review of radioimmunotherapy in cancer treatment, exploring both current practices and future directions. Radioimmunotherapy involves the use of radioactive substances coupled with antibodies to target and destroy cancer cells. The review delves into the efficacy of this approach in various cancer types and discusses ongoing research aimed at enhancing its effectiveness [...]

Media Type
    Buy from

    Price may vary by retailers

    Work TypeBook Chapter
    Published inThe Latest Innovative Approaches in Radiation Therapy
    First Page133
    Last Page156
    DOIhttps://doi.org/10.69860/nobel.9786053359425.6
    Page Count24
    Copyright HolderNobel Tıp Kitabevleri
    Licensehttps://nobelpub.com/publish-with-us/copyright-and-licensing
    This section presents a review of radioimmunotherapy in cancer treatment, exploring both current practices and future directions. Radioimmunotherapy involves the use of radioactive substances coupled with antibodies to target and destroy cancer cells. The review delves into the efficacy of this approach in various cancer types and discusses ongoing research aimed at enhancing its effectiveness and reducing side effects. Additionally, the section provides insights into potential advancements and innovations in radioimmunotherapy that may shape the future of cancer treatment.

    Duriye Ozturk (Author)
    Assistant Professor, Afyonkarahisar Sağlık Bilimleri Üniversitesi
    https://orcid.org/0000-0002-3265-2797
    3Assistant Prof. Dr. Düriye Öztürk completed her education at Akdeniz University, School of Medicine, specializing in Radiation Oncology from 2002 to 2009, following her undergraduate studies at Akdeniz University, School of Medicine from 1990 to 1997. Currently, she serves as the Head of the Department of Radiation Oncology at Afyonkarahisar Health Sciences University, Faculty of Medicine, in Afyonkarahisar, Turkey, a position she has held since 2014. Her impactful contributions to the field are evident through the publication of over 30 research articles, oral and poster presentations, and reviews. Dr. Öztürk is also an esteemed member of the Turkish Association of Radiation Oncology.

    • Grossbard ML, Press OW, Appelbaum FR, Bernstein ID, Nadler LM. Monoclonal antibody-based therapies of leukemia and lymphoma. Blood. 1992; 80(4):863– 878. [PubMed: 1498329]

    • Sharkey RM, Goldenberg DM. Perspectives on cancer therapy with radiolabeled monoclonal antibodies. J Nucl Med. 2005; 46(Suppl 1):S115–S127.

    • Weiner LM, Surana R, Wang S. Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nat Rev Immunol. 2010; 10(5):317–327

    • Nelson AL, Dhimolea E, Reichert JM. Development trends for human monoclonal antibody therapeutics. Nat Rev Drug Discov. 2010; 9(10):767–774

    • Topalian SL, Weiner GJ, Pardoll DM. Cancer immunotherapy comes of age. J Clin Oncol. 2011;29(36):4828–36

    • Kfoury M, Disdero V, Vicier C, Le Saux O, Gougis P, Sajous C, et al. Immune checkpoints inhibitors: recent data from ASCO’s meeting 2017 and perspectives. Bull Cancer. 2018;105(7–8):686–95

    • Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10

    • Demaria S, Golden EB, Formenti SC. Role of local radiation therapy in cancer immunotherapy. JAMA Oncol. 2015;1(9):1325–32

    • Wennerberg E, Lhuillier C, Vanpouille-Box C, Pilones KA, García-Martínez E, et al. Barriers to radiation-induced in situ tumor vaccination. Front Immunol. 2017;8:22

    • Yamazaki T, Kirchmair A, Sato A, et al. Mitochondrial DNA drives abscopal responses to radiation that are inhibited by autophagy. Nat Immunol 2020;21:1160– 71

    • Vanpouille-Box C, Alard A, Aryankalayil MJ, et al. DNA exonuclease TREX1 regulates radiotherapy-induced tumour immunogenicity. Nat Commun 2017;8: 15618

    • Lejeune P, Cruciani V, Berg-Larsen A, et al. Immunostimulatory effects of targeted thorium-227 conjugates as single agent and in combination with anti- PD-L1 therapy. J Immunother Cancer 2021;9:e002387

    • Pressman D, Day ED, Blau M. The use of paired labeling in the determination of tumor-localizing antibodies. Cancer Res. 1957;17:845–850

    • Bale WF, Spar IL, Goodland RL. Experimental radiation therapy of tumors with I-131-carrying antibodies to fibrin. Cancer Res. 1960;20:1488–1494

    • Goldenberg DM. Imaging and therapy of cancer with radiolabeled monoclonal antibodies. Prog Clin Biol Res. 1989;288:413–427.

    • Larson SM, Carrasquillo JA, Reynolds JC. Radioimmunodetection and radioimmunotherapy. Cancer Invest. 1984;2:363–381

    • Kim EE, Deland FH, Casper S, Corgan RL, Primus FJ, Goldenberg DM. Radioimmunodetection of colorectal cancer. Cancer. 1980;45:1243–1247

    • Reardan DT, Meares CF, Goodwin DA, et al. Antibodies against metal chelates. Nature. 1985;316:265–268

    • Goodwin DA, Meares CF, McTigue M, David GS. Monoclonal antibody hapten adiopharmaceutical delivery. Nucl Med Commun. 1986;7:569–580

    • Goodwin DA, Meares CF, McCall MJ, McTigue M, Chaovapong W. Pre-targeted immunoscintigraphy of murine tumors with indium-111-labeled bifunctional haptens. J Nucl Med. 1988;29:226–234.

    • Stickney DR, Anderson LD, Slater JB, et al. Bifunctional antibody: a binary radiopharmaceutical delivery system for imaging colorectal carcinoma. Cancer Res. 1991;51:6650–6655

    • Hnatowich DJ, Virzi F, Rusckowski M. Investigations of avidin and biotin for imaging applications. J Nucl Med. 1987;28:1294–1302.

    • Pimm MV, Fells HF, Perkins AC, Baldwin RW. Iodine-131 and indium-111 labelled avidin and streptavidin for pre-targetted immunoscintigraphy with biotinylated anti-tumour monoclonal antibody. Nucl Med Commun. 1988;9:931– 941.

    • Wilbur DS, Hamlin DK, Meyer DL, et al. Streptavidin in antibody pretargeting.3. Comparison of biotin binding and tissue localization of 1,2-cyclohexanedione and succinic anhydride modified recombinant streptavidin. Bioconjug Chem. 2002;13:611–620.

    • Wilbur DS, Stayton PS, To R, et al. Streptavidin in antibody pretargeting: comparison of a recombinant streptavidin with two streptavidin mutant proteins and two commercially available streptavidin proteins. Bioconjug Chem. 1998;9:100–107.

    • Kalofonos HP, Rusckowski M, Siebecker DA, et al. Imaging of tumor in patients with indium-111-labeled biotin and streptavidin-conjugated antibodies: preliminary communication. J Nucl Med. 1990;31:1791–1796.

    • Paganelli G, Magnani P, Zito F, et al. Three-step monoclonal antibody tumor targeting in carcinoembryonic antigen-positive patients. Cancer Res. 1991;51:5960–5966

    • Kraeber-Bodere F, Rousseau C, Bodet-Milin C, et al. A pretargeting system for tumor PET imaging and radioimmunotherapy. Front Pharmacol. 2015;6:54.

    • Divgi C, Carrasquillo JA, Meredith R, et al. Overcoming barriers to radiopharmaceu tical therapy (RPT): an overview from the NRG-NCI working group on dosimetry of radiopharmaceutical therapy. Int J Radiat Oncol Biol Phys. 2021;109:905–912

    • Sgouros G, Bodei L, McDevitt MR, Nedrow JR. Radiopharmaceutical therapy in cancer: clinical advances and challenges. Nat Rev Drug Discov. 2020;19:589–608

    • Larson SM, Carrasquillo JA, Cheung NK, Press OW. Radioimmunotherapy of human tumours. Nat Rev Cancer. 2015;15:347–360

    • Paganelli G, Chinol M, Grana C, et al. Therapy trials in cancer patients using an improved 3-step pretargeting approach. In: Bergmann H, Kroiss A, Sinzinger H, eds. Radioactive Isotopes in Clinical Medicine and Research: Springer; 1997: 513–517

    • Axworthy D, Beaumier P, Bottino B, et al. Preclinical optimization of pretargeted radioimmunotherapy components: high efficiency, curative 90Y delivery to mouse tumor xenografts. Tumor Targeting. 1996;2:156.

    • Murtha A, Weiden P, Knox S, et al. Phase I dose escalation trial of pretargeted radioimmunotherapy (PRIT) with 90yttrium. Proc Am Soc Clin Oncol [abstract]. 1998;17:438.

    • Weiden PL, Breitz HB, Press O, et al. Pretargeted radioimmunotherapy (PRIT) for treatment of non-Hodgkin’s lymphoma (NHL): initial phase I/II study results. Cancer Biother Radiopharm. 2000;15:15–29.

    • Breitz HB, Fisher DR, Goris ML, et al. Radiation absorbed dose estimation for 90Y-DOTA-biotin with pretargeted NR-LU-10/streptavidin. Cancer Biother Radiopharm. 1999;14:381–395

    • Press OW, Appelbaum F, Martin P, et al. Phase II trial of 131I-B1 (anti-CD20) antibody therapy with autologous stem cell transplantation for relapsed B cell lymphomas. Lancet. 1995;346:336–340.

    • Witzig TE, Gordon LI, Cabanillas F, et al. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma. J Clin Oncol. 2002;20:2453–2463.

    • Breitz HB, Weiden PL, Beaumier PL, et al. Clinical optimization of pretargeted radioimmunotherapy with antibody-streptavidin conjugate and 90Y-DOTAbiotin. J Nucl Med. 2000;41:131–140.

    • Kraeber-Bodere F, Bardet S, Hoefnagel CA, et al. Radioimmunotherapy in medullary thyroid cancer using bispecific antibody and iodine 131-labeled bivalent hapten: preliminary results of a phase I/II clinical trial. Clin Cancer Res. 1999; 5(suppl):3190s–3198s.

    • Vuillez J-P, Kraeber-Bodere F, Moro D, et al. Radioimmunotherapy of small cell lung carcinoma with the two-step method using a bispecific anticarcinoembryonic antigen/anti-diethylenetriaminepentaacetic acid (DTPA) antibody and iodine-131 Di-DTPA hapten: results of a phase I/II trial. Clin Cancer Res. 1999;5(suppl):3259s–3267s

    • Paganelli G, Ferrari M, Ravasi L, et al. Intraoperative avidination for radionuclide therapy: a prospective new development to accelerate radiotherapy in breast cancer. Clin Cancer Res. 2007;13:5646s–5651s.

    • Petronzelli F, Pelliccia A, Anastasi AM, et al. Therapeutic use of avidin is not hampered by antiavidin antibodies in humans. Cancer Biother Radiopharm. 2010;25:563–570.

    • DeNardo SJ, DeNardo GL, O’Grady LF, et al. Treatment of B cell malignancies with 131I Lym-1 monoclonal antibodies. Int J Cancer Suppl. 1988; 3:96–101

    • DeNardo SJ, DeNardo GL, O’Grady LF, et al. Treatment of a patient with B cell lymphoma by I-131 LYM-1 monoclonal antibodies. Int J Biol Markers. 1987; 2(1):49–53

    • Press OW, Eary JF, Badger CC, et al. Treatment of refractory non-Hodgkin’s lymphoma with radiolabeled MB-1 (anti-CD37) antibody. J Clin Oncol. 1989; 7(8):1027–1038

    • Goldenberg DM, Horowitz JA, Sharkey RM, et al. Targeting, dosimetry, and radioimmunotherapy of B-cell lymphomas with iodine-131-labeled LL2 monoclonal antibody. J Clin Oncol. 1991; 9(4): 548–564

    • Kaminski MS, Zasadny KR, Francis IR, et al. Radioimmunotherapy of B-cell lymphoma with 131Ianti-B1 (anti-CD20) antibody. N Engl J Med. 1993; 329(7):459–465

    • Press OW, Eary JF, Appelbaum FR, et al. Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support. N Engl J Med. 1993; 329(17):1219–1224

    • Knox SJ, Goris ML, Trisler K, et al. Yttrium-90-labeled anti-CD20 monoclonal antibody therapy of recurrent B-cell lymphoma. Clin Cancer Res. 1996; 2(3):457– 470

    • Witzig TE, White CA, Wiseman GA, et al. Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20+ B-cell non- Hodgkin’s lymphoma. J Clin Oncol. 1999; 17(12):3793–3803

    • Kaminski MS, Zasadny KR, Francis IR, et al. Iodine-131-anti-B1 radioimmunotherapy for B-cell lymphoma. J Clin Oncol. 1996; 14(7):1974–1981

    • Koral KF, Dewaraja Y, Clarke LA, et al. Tumor-absorbed-dose estimates versus response in tositumomab therapy of previously untreated patients with follicular non-Hodgkin’s lymphoma: preliminary report. Cancer Biother Radiopharm. 2000; 15(4):347–355

    • Sgouros G, Squeri S, Ballangrud AM, et al. Patient-specific, 3-dimensional dosimetry in nonHodgkin’s lymphoma patients treated with 131I-anti-B1 antibody: assessment of tumor doseresponse. J Nucl Med. 2003; 44(2):260–268

    • Sharkey RM, Brenner A, Burton J, et al. Radioimmunotherapy of non-Hodgkin’s lymphoma with 90Y-DOTA humanized anti-CD22 IgG (90Y-epratuzumab): do tumor targeting and dosimetry predict therapeutic response? J Nucl Med. 2003; 44(12):2000–2018

    • Koral KF, Dewaraja Y, Li J, et al. Update on hybrid conjugate-view SPECT tumor dosimetry and response in 131I-tositumomab therapy of previously untreated lymphoma patients. J Nucl Med. 2003; 44(3):457–464

    • Cardarelli PM, Quinn M, Buckman D, et al. Binding to CD20 by anti-B1 antibody or F(ab’)2 is sufficient for induction of apoptosis in B-cell lines. Cancer Immunol Immunother.2002; 51(1):15–24

    • Du Y, Honeychurch J, Cragg MS, et al. Antibody-induced intracellular signaling works in combination with radiation to eradicate lymphoma in radioimmunotherapy. Blood. 2004; 103(4): 1485–1494

    • Hernandez MC, Knox SJ. Radiobiology of radioimmunotherapy: targeting CD20 B-cell antigen in non-Hodgkin’s lymphoma. Int J Radiat Oncol Biol Phys. 2004; 59(5):1274–1287

    • Kapadia NS, Engles JM, Wahl RL. In vitro evaluation of radioprotective and radiosensitizing effects of rituximab. J Nucl Med. 2008; 49(4):674–678

    • Ivanov A, Krysov S, Cragg MS, Illidge T. Radiation therapy with tositumomab (B1) anti-CD20 monoclonal antibody initiates extracellular signal-regulated kinase/mitogen-activated protein kinase-dependent cell death that overcomes resistance to apoptosis. Clin Cancer Res. 2008; 14(15):4925–4934

    • Witzig TE, Molina A, Gordon LI, et al. Long-term responses in patients with recurring or refractory B-cell non-Hodgkin lymphoma treated with yttrium90 ibritumomab tiuxetan. Cancer. 2007; 109(9):1804–1810

    • Buchegger F, Antonescu C, Delaloye AB, et al. Long-term complete responses after 131Itositumomab therapy for relapsed or refractory indolent non-Hodgkin’s lymphoma. Br J Cancer. 2006; 94(12):1770–1776

    • Bennett JM, Kaminski MS, Leonard JP, et al. Assessment of treatment-related myelodysplastic syndromes and acute myeloid leukemia in patients with nonHodgkin lymphoma treated with tositumomab and iodine I131 tositumomab. Blood. 2005; 105(12):4576–4582.

    • Czuczman MS, Emmanouilides C, Darif M, et al. Treatment-related myelodysplastic syndrome and acute myelogenous leukemia in patients treated with ibritumomab tiuxetan radioimmunotherapy. J Clin Oncol. 2007; 25(27):4285–4292

    • Ansell SM, Schilder RJ, Pieslor PC, et al. Antilymphoma treatments given subsequent to yttrium90 ibritumomab tiuxetan are feasible in patients with progressive non-Hodgkin’s lymphoma: a review of the literature. Clin Lymphoma. 2004; 5(3):202–204.

    • Kaminski MS, Tuck M, Estes J, et al. 131I-tositumomab therapy as initial treatment for follicular lymphoma. N Engl J Med. 2005; 352(5):441–449.

    • Kaminski MS, Estes J, Zasadny KR, et al. Radioimmunotherapy with iodine 131I tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: updated results and long-term follow-up of the University of Michigan experience. Blood. 2000; 96(4):1259–1266.

    • Kaminski MS, Radford JA, Gregory SA, et al. Re-treatment with I-131 tositumomab in patients with non-Hodgkin’s lymphoma who had previously responded to I-131 tositumomab. J Clin Oncol. 2005; 23(31):7985–7993.

    • Leonard JP, Coleman M, Kostakoglu L, et al. Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I131 tositumomab for untreated follicular lymphoma. J Clin Oncol. 2005; 23(24):5696–5704

    • Press OW, Unger JM, Braziel RM, et al. Phase II trial of CHOP chemotherapy followed by tositumomab/iodine I-131 tositumomab for previously untreated follicular non-Hodgkin’s lymphoma: five-year follow-up of Southwest Oncology Group Protocol S9911. J Clin Oncol. 2006; 24(25):4143–4149

    • Morschhauser F, Radford J, Van Hoof A, et al. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol. 2008; 26(32):5156–5164.

    • Zinzani PL, Tani M, Fanti S, et al. A Phase II trial of CHOP chemotherapy followed by yttrium90 ibritumomab tiuxetan (Zevalin) for previously untreated elderly diffuse large B-cell lymphoma patients. Ann Oncol. 2008; 19(4):769–773

    • Russo AL, Chen YH, Martin NE, et al. Low-dose involved-field radiation in the treatment of non-hodgkin lymphoma: predictors of response and treatment failure. Int J Radiat Oncol Biol Phys 2013; 86:121.

    • Davis TA, Kaminski MS, Leonard JP, et al. The radioisotope contributes significantly to the activity of radioimmunotherapy. Clin Cancer Res 2004; 10:7792.

    • Wiseman GA, Gordon LI, Multani PS, et al. Ibritumomab tiuxetan radioimmunotherapy for patients with relapsed or refractory non-Hodgkin lymphoma and mild thrombocytopenia: a phase II multicenter trial. Blood 2002; 99:4336.

    • Gordon LI, Molina A, Witzig T, et al. Durable responses after ibritumomab tiuxetan radioimmunotherapy for CD20+ B-cell lymphoma: long-term follow-up of a phase 1/2 study. Blood 2004; 103:4429.

    • Emmanouilides C, Witzig TE, Wiseman GA, et al. Safety and efficacy of yttrium-90 ibritumomab tiuxetan in older patients with non-Hodgkin’s lymphoma. Cancer Biother Radiopharm 2007; 22:684.

    • Jurcic JG, Scheinberg DA. Radioimmunotherapy of hematological cancer: problems and progress. Clin Cancer Res. 1995; 1(12):1439–1446

    • McDevitt MR, Sgouros G, Finn RD, et al. Radioimmunotherapy with α-emitting nuclides. Eur J Nucl Med. 1998; 25(9):1341–1351

    • Nikula TK, McDevitt MR, Finn RD, et al. α-emitting bismuth cyclohexylbenzyl DTPA constructs of recombinant humanized anti-CD33 antibodies: pharmacokinetics, bioactivity, toxicity and chemistry. J Nucl Med. 1999; 40(1):166–176

    • Sgouros G, Ballangrud AM, Jurcic JG, et al. Pharmacokinetics and dosimetry of an α-particle emitter labeled antibody: 213Bi-HuM195 (anti-CD33) in patients with leukemia. J Nucl Med. 1999; 40(11):1935–1946

    • Jurcic JG, Larson SM, Sgouros G, et al. Targeted α particle immunotherapy for myeloid leukemia.Blood. 2002; 100(4):1233–1239.

    • Borchardt PE, Yuan RR, Miederer M, McDevitt MR, Scheinberg DA. Targeted actinium-225 in vivo generators for therapy of ovarian cancer. Cancer Res. 2003; 63(16):5084–5090

    • Yao Z, Zhang M, Garmestani K, et al. Pretargeted α emitting radioimmunotherapy using 213Bi 1,4,7,10-tetraazacyclododecane-N, N’, N’, N’-tetraacetic acid-biotin. Clin Cancer Res. 2004; 10(9): 3137–3146

    • Jaggi JS, Seshan SV, McDevitt MR, et al. Renal tubulointerstitial changes after internal irradiation with α-particle-emitting actinium daughters. J Am Soc Nephrol. 2005; 16(9):2677–2689

    • Jaggi JS, Seshan SV, McDevitt MR, et al. Mitigation of radiation nephropathy after internal αparticle irradiation of kidneys. Int J Radiat Oncol Biol Phys. 2006; 64(5):1503–1512

    • Song H, Hobbs RF, Vajravelu R, et al. Radioimmunotherapy of breast cancer metastases with αparticle emitter 225Ac: comparing efficacy with 213Bi and 90Y. Cancer Res. 2009; 69(23):8941–8948.

    • Kraeber-Bodéré F, Rousseau C, Bodet-Milin C, et al. Targeting, toxicity, and efficacy of 2-step, pretargeted radioimmunotherapy using a chimeric bispecific antibody and 131I-labeled bivalent hapten in a phase I optimization clinical trial. J Nucl Med 2006; 47:247.

    • Chatal JF, Campion L, Kraeber-Bodéré F, et al. Survival improvement in patients with medullary thyroid carcinoma who undergo pretargeted anticarcinoembryonic- antigen radioimmunotherapy: a collaborative study with the French Endocrine Tumor Group. J Clin Oncol 2006; 24:1705.

    • Iten F, Müller B, Schindler C, et al. Response to [90Yttrium-DOTA]-TOC treatment is associated with long-term survival benefit in metastasized medullary thyroid cancer: a phase II clinical trial. Clin Cancer Res 2007; 13:6696.

    • Grossrubatscher E, Fanciulli G, Pes L, et al. Advances in the Management of Medullary Thyroid Carcinoma: Focus on Peptide Receptor Radionuclide Therapy. J Clin Med 2020;9.

    • Tempero M, Leichner P, Dalrymple G, et al. High-dose therapy with iodine-131- labeled monoclonal antibody CC49 in patients with gastrointestinal cancers: a Phase I trial. J Clin Oncol.1997; 15(4):1518-1528

    • Wong JYC, Chu DZ, Yamauchi DM, et al. A Phase I radioimmunotherapy trial evaluating 90yttrium-labeled anti-carcinoembryonic antigen (CEA) chimeric T84.66 in patients with metastatic CEA-producing malignancies. Clin Cancer Res. 2000; 6(10):3855–3863

    • Tempero M, Leichner P, Baranowska-Kortylewicz J, et al. High-dose therapy with 90yttriumlabeled monoclonal antibody CC49: a Phase I trial. Clin Cancer Res. 2000; 6(8):3095-3102

    • Wong JY, Shibata S, Williams LE, et al. A Phase I trial of 90Y-anti-carcinoembryonic antigenchimeric T84.66 radioimmunotherapy with 5-fluorouracil in patients with metastatic colorectal cancer. Clin Cancer Res. 2003; 9(16 Pt 1):5842–5852

    Share This Chapter!