Spescial Issues

Progress in Cancer Bio-immunotherapy

  • WU Yanhong ,
  • WANG Huiru ,
  • DENG Zhenling ,
  • GE Keli ,
  • ZHANG Shuren
  • Department of Immunology, Cancer Institute & Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100021, China

Received date: 2014-08-12

  Revised date: 2014-08-15

  Online published: 2014-09-26


The cancer immunoediting theory dipicts the significance of immune system in cancer development and progression. The success of antibodies targeting the suppressive immune component has emphasized the importance and effectiveness of immunotherapy in cancer treatment. Combined with surgery, radiotherapy and chemotherapy, immunotherapy including antibody therapy, cytokine, cancer vaccine, adoptive immune cell transfer and oncolytic virus is a potential and promising treatment for cancer. This review will mainly introduce the progress in antibody therapy, cancer vaccine, adoptive cellular immunotherapy and oncolytic virus, as well as point out the problems and future development in cancer bio-immunotherapy.

Cite this article

WU Yanhong , WANG Huiru , DENG Zhenling , GE Keli , ZHANG Shuren . Progress in Cancer Bio-immunotherapy[J]. Science & Technology Review, 2014 , 32(26) : 27 -36 . DOI: 10.3981/j.issn.1000-7857.2014.26.003


[1] McNutt M. Cancer immunotherapy[J]. Science, 2013, 342: 1432-1433.
[2] Schreiber R D, Old L J, Smyth M J. Cancer immunoediting: Integrating immunity's roles in cancer suppression and promotion[J]. Science, 2011, 331(6024): 1565-1570.
[3] Vacchelli E, Aranda F, Eggermont A, et al. Trial watch: Tumor-targeting monoclonal antibodies in cancer therapy[J]. Oncoimmunology, 2014, 3 (1): e27048-1-20.
[4] Li S, Schmitz K R, Jeffrey P D, et al. Structural basis for inhibition of the epidermal growth factor receptor by cetuximab[J]. Cancer Cell, 2005, 7(4): 301-311.
[5] van Cutsem E, Kohne C H, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer[J]. The New England Journal of Medicine, 2009, 360(14):1408-1417.
[6] Kuenen B, Witteveen P O, Ruijter R, et al. A phase i pharmacologic study of necitumumab (imc- 11f8), a fully human igg1 monoclonal antibody directed against egfr in patients with advanced solid malignancies[J]. Clinical Cancer Research, 2010, 16(6): 1915-1923.
[7] Ellis L M, Hicklin D J. Vegf-targeted therapy: Mechanisms of antitumour activity[J]. Nature Reviews Cancer, 2008, 8(8): 579-591.
[8] Junttila M R, de Sauvage F J. Influence of tumour micro-environment heterogeneity on therapeutic response[J]. Nature, 2013, 501(7467): 346- 354.
[9] Vedi A, Ziegler D S. Antibody therapy for pediatric leukemia[J]. Frontiers in Oncology, 2014, 4: 82.
[10] Sarnaik A A, Weber J S. Recent advances using anti-ctla-4 for the treatment of melanoma[J]. The Cancer Journal, 2009, 15(3): 169-173.
[11] Brahmer J R, Drake C G, Wollner I, et al. Phase i study of singleagent anti-programmed death-1 (mdx-1106) in refractory solid tumors: Safety, clinical activity, pharmacodynamics, and immunologic correlates[J]. Journal of Clinical Oncology, 2010, 28(19): 3167-3175.
[12] Kirkwood J M, Tarhini A A, Panelli M C, et al. Next generation of immunotherapy for melanoma[J]. Journal of Clinical Oncology, 2008, 26(20): 3445-3455.
[13] Weiner L M, Surana R, Wang S. Monoclonal antibodies: Versatile platforms for cancer immunotherapy[J]. Nature Reviews Immunology, 2010, 10(5): 317-327.
[14] Grutter C, Wilkinson T, Turner R, et al. A cytokine- neutralizing antibody as a structural mimetic of 2 receptor interactions[J]. Proceedings of the National Academy of Sciences, 2008, 105(51): 20251-20256.
[15] ArandaF,VacchelliE,EggermontA,etal.Trialwatch: Immunostimulatory monoclonal antibodies in cancer therapy[J]. Oncoimmunology, 2014, 3 (1): e27297-1-11.
[16] Scott A M, Wolchok J D, Old L J. Antibody therapy of cancer[J]. Nature Reviews Cancer, 2012, 12(4): 278-287.
[17] Baldo B A. Adverse events to monoclonal antibodies used for cancer therapy: Focus on hypersensitivity responses[J]. Oncoimmunology, 2013, 2(10): e26333-1-15.
[18] Palucka K, Banchereau J. Dendritic- cell- based therapeutic cancer vaccines[J]. Immunity, 2013, 39(1): 38-48.
[19] Mocellin S, Mandruzzato S, Bronte V, et al. Part i: Vaccines for solid tumours[J]. The Lancet Oncology, 2004, 5(11): 681-689.
[20] Aranda F, Vacchelli E, Eggermont A, et al. Trial watch: Peptide vaccines in cancer therapy[J]. Oncoimmunology, 2013, 2(12): e26621- 1-11.
[21] Drake C G, Lipson E J, Brahmer J R. Breathing new life into immunotherapy: Review of melanoma, lung and kidney cancer[J]. Nature Reviews Clinical Oncology, 2014, 11(1): 24-37.
[22] Cuppens K, Vansteenkiste J. Vaccination therapy for non-small-cell lung cancer[J]. Current Opinion in Oncology, 2014, 26(2): 165-170.
[23] Anguille S, Smits E L, Lion E, et al. Clinical use of dendritic cells for cancer therapy[J]. The Lancet Oncology, 2014, 15(7): e257-e267.
[24] Ruiz R, Hunis B, Raez L E. Immunotherapeutic agents in non-smallcell lung cancer finally coming to the front lines[J]. Current Oncology Reports, 2014, 16(9): 400-1-10.
[25] Herrera Z M, Ramos T C. Pilot study of a novel combination of two therapeutic vaccines in advanced non-small-cell lung cancer patients[J]. Cancer Immunology, Immunotherapy, 2014, 63(7): 737-747.
[26] McCarthy F, Roshani R, Steele J, et al. Current clinical immunotherapy targets in advanced nonsmall cell lung cancer (nsclc) [J]. Journal of Leukocyte Biology, 2013, 94(6): 1201-1206.
[27] Karan D, Holzbeierlein J M, Van Veldhuizen P, et al. Cancer immunotherapy: A paradigm shift for prostate cancer treatment[J]. Nature Reviews Urology, 2012, 9(7): 376-385.
[28] Geary S M, Lemke C D, Lubaroff D M, et al. Proposed mechanisms of action for prostate cancer vaccines[J]. Nature Reviews Urology, 2013, 10(3): 149-160.
[29] van den Boorn J G, Hartmann G. Turning tumors into vaccines: Coopting the innate immune system[J]. Immunity, 2013, 39(1): 27-37.
[30] Jacobs J J, Snackey C, Geldof A A, et al. Inefficacy of therapeutic cancer vaccines and proposed improvements. Casus of prostate cancer[J]. Anticancer Research, 2014, 34(6): 2689-2700.
[31] Xu L W, Chow K K, Lim M, et al. Current vaccine trials in glioblastoma: A review[J]. Journal of Immunology Research, 2014, 2014: 796856-1-10.
[32] Kalos M, June C H. Adoptive t cell transfer for cancer immunotherapy in the era of synthetic biology[J]. Immunity, 2013, 39(1): 49-60.
[33] Weber J S. At the bedside: Adoptive cell therapy for melanomaclinical development[J]. Journal of Leukocyte Biology, 2014, 95(6): 875-882.
[34] Besser M J, Shapira-Frommer R, Itzhaki O, et al. Adoptive transfer of tumor-infiltrating lymphocytes in patients with metastatic melanoma: Intent- to- treat analysis and efficacy after failure to prior immunotherapies[J]. Clinical Cancer Research, 2013, 19(17): 4792- 4800.
[35] Kirk R. Immunotherapy: Adoptive cell therapy simplified[J]. Nature Reviews Clinical Oncology, 2013, 10(7): 368.
[36] Dudley M E, Gross C A, Somerville R P, et al. Randomized selection design trial evaluating CD8+-enriched versus unselected tumorinfiltrating lymphocytes for adoptive cell therapy for patients with melanoma[J]. Journal of Clinical Oncology, 2013, 31(17): 2152-2159.
[37] Mesiano G, Todorovic M, Gammaitoni L, et al. Cytokine- induced killer (cik) cells as feasible and effective adoptive immunotherapy for the treatment of solid tumors[J]. Expert Opinion on Biological Therapy, 2012, 12(6): 673-684.
[38] Liu L, Zhang W, Qi X, et al. Randomized study of autologous cytokine-induced killer cell immunotherapy in metastatic renal carcinoma[J]. Clinical Cancer Research, 2012, 18(6): 1751-1759.
[39] Zhao H, Fan Y, Li H, et al. Immunotherapy with cytokine-induced killer cells as an adjuvant treatment for advanced gastric carcinoma: A retrospective study of 165 patients[J]. Cancer Biotherapy & Radiopharmaceuticals, 2013, 28: 303-309.
[40] Yu X, Zhao H, Liu L, et al. A randomized phase ii study of autologous cytokine-induced killer cells in treatment of hepatocellular carcinoma[J]. Jornal of Clinical Immunology, 2014, 34(2): 194-203.
[41] Li X D, Xu B, Wu J, et al. Review of Chinese clinical trials on cik cell treatment for malignancies[J]. Clinical & Translational Oncology, 2012, 14(2): 102-108.
[42] Ren J, Di L, Song G, et al. Selections of appropriate regimen of highdose chemotherapy combined with adoptive cellular therapy with dendritic and cytokine-induced killer cells improved progression-free and overall survival in patients with metastatic breast cancer: Reargument of such contentious therapeutic preferences[J]. Clinical & Translational Oncology, 2013, 15(10): 780-788.
[43] Zhao M, Li H, Li L, et al. Effects of a gemcitabine plus platinum regimen combined with a dendritic cell-cytokine induced killer immunotherapy on recurrence and survival rate of non-small cell lung cancer patients[J]. Experimental & Therapeutic Medicine, 2014, 7(5): 1403-1407.
[44] Shi S B, Tang X Y, Tian J, et al. Efficacy of erlotinib plus dendritic cells and cytokine- induced killer cells in maintenance therapy of advanced non- small cell lung cancer[J]. Journal of Immunotherapy, 2014, 37(4): 250-255.
[45] Gao D, Li C, Xie X, et al. Autologous tumor lysate-pulsed dendritic cell immunotherapy with cytokine-induced killer cells improves survival in gastric and colorectal cancer patients[J]. PLoS One, 2014, 9 (4): e93886-1-9.
[46] Wang Q J, Wang H, Pan K, et al. Comparative study on anti-tumor immune response of autologous cytokine- induced killer (cik) cells, dendritic cells-cik (dc-cik), and semi-allogeneic dc-cik[J]. Chinese Journal of Cancer, 2010, 29(7): 641-648.
[47] Aranda F, Vacchelli E, Obrist F, et al. Trial watch: Adoptive cell transfer for anticancer immunotherapy[J]. Oncoimmunology, 2014, 3: e28344-1-13.
[48] Fisher J P, Heuijerjans J, Yan M, et al. Gammadelta t cells for cancer immunotherapy: A systematic review of clinical trials[J]. Oncoimmunology, 2014, 3(1): e27572-1-10.
[49] Rubnitz J E, Inaba H, Ribeiro R C, et al. Nkaml: A pilot study to determine the safety and feasibility of haploidentical natural killer cell transplantation in childhood acute myeloid leukemia[J]. Journal of Clinical Oncology, 2010, 28(6): 955-959.
[50] Miller J S, Soignier Y, Panoskaltsis- Mortari A, et al. Successful adoptive transfer and in vivo expansion of human haploidentical nk cells in patients with cancer[J]. Blood, 2005, 105(8): 3051-3057.
[51] Davies J O, Stringaris K, Barrett J A, et al. Opportunities and limitations of natural killer cells as adoptive therapy for malignant disease[J]. Cytotherapy, 2014, doi: 10.1016/j.jcyt.2014.03.009.
[52] Humphries C. Adoptive cell therapy: Honing that killer instinct[J]. Nature, 2013, 504(7480): 13-15.
[53] Kershaw M H, Westwood J A, Slaney C Y, et al. Clinical application of genetically modified t cells in cancer therapy[J]. Clinical & Translational Immunology, 2014, 3: e16-1-7.
[54] Maus M V, Grupp S A, Porter D L, et al. Antibody-modified t cells: Cars take the front seat for hematologic malignancies[J]. Blood, 2014, 123(17): 2625-2635.
[55] Han E Q, Li X L, Wang C R, et al. Chimeric antigen receptorengineered t cells for cancer immunotherapy: Progress and challenges[J]. Journal of Hematology & Oncology, 2013, 6: 47-1-7.
[56] Raval R R, Sharabi A B, Walker A J, et al. Tumor immunology and cancer immunotherapy: Summary of the 2013 sitc primer[J]. Journal for Immunotherapy of Cancer, 2014, 2: 141-152.
[57] DeFrancesco L. Car-t cell therapy seeks strategies to harness cytokine storm[J]. Nature Biotechnology, 2014, 32(7): 604.
[58] Tey S-K. Adoptive t-cell therapy: Adverse events and safety switches[J]. Clinical & Translational Immunology, 2014, 3: e17-1-7.
[59] You L, He B, Xu Z, et al. Future directions: Oncolytic viruses[J]. Clinical Lung Cancer, 2004, 5(4): 226-230.
[60] Prestwich R J, Errington F, Diaz R M, et al. The case of oncolytic viruses versus the immune system: Waiting on the judgment of solomon[J]. Human Gene Therapy, 2009, 20(10): 1119-1132.
[61] Kaufman H L, Kim D W, DeRaffele G, et al. Local and distant immunity induced by intralesional vaccination with an oncolytic herpes virus encoding gm- csf in patients with stage iiic and iv melanoma[J]. Annals of Surgical Oncology, 2010, 17(3): 718-730.
[62] Atherton M J, Lichty B D. Evolution of oncolytic viruses: Novel strategies for cancer treatment[J]. Immunotherapy, 2013, 5(11): 1191- 1206.
[63] Kaufman H L, Bines S D. Optim trial: A phase iii trial of an oncolytic herpes virus encoding gm-csf for unresectable stage iii or iv melanoma[J]. Future Oncol, 2010, 6(6): 941-949.
[64] Thorne S H. Immunotherapeutic potential of oncolytic vaccinia virus[J]. Frontiers in Oncology, 2014, 4: 155.
[65] Moehler M, Goepfert K, Heinrich B, et al. Oncolytic virotherapy as emerging immunotherapeutic modality: Potential of parvovirus h-1[J]. Frontiers in Oncology, 2014, 4: 92.
[66] Finke J H, Rayman P A, Ko J S, et al. Modification of the tumor microenvironment as a novel target of renal cell carcinoma therapeutics[J]. The Cancer Journal, 2013, 19(4): 353-364.
[67] Golden E B, Pellicciotta I, Demaria S, et al. The convergence of radiation and immunogenic cell death signaling pathways[J]. Frontiers in Oncology, 2012, 2: 88.
[68] Hellevik T, Martinez-Zubiaurre I. Radiotherapy and the tumor stroma: The importance of dose and fractionation[J]. Frontiers in Oncology, 2014, 4: 1.
[69] Sachamitr P, Hackett S, Fairchild P J. Induced pluripotent stem cells: Challenges and opportunities for cancer immunotherapy[J]. Frontiers in Immunology, 2014, 5: 176.