Recent Developments in Gene Therapy and Immunotherapy
Received Date: Jun 19, 2018 / Accepted Date: Jul 16, 2018 / Published Date: Jul 24, 2018
In 2017, 8 of the 10 most popular drugs belong to large molecules such as antibodies (Humira/Adalimumab, Remicade/infiximab, Qituxan/Rituximab, Avastin/Bevasizumab, Herceptin/Trastuzumab, Opdivo/Nivolumab) or proteins (Enbrel/Etnaercept and Eylea/ Aflibercept). The only two small molecule drugs are Revlimid/ Lenalidomide and Xarelto/Rivaroxaban.
The editor intends to start a new column to summarize the recent developments in gene therapy and immunotherapy in an outline format every 2-3 months.
Here is the outline format of recent developments as follows:
Motzer et al. reported that the combination of Nivolumab (PD-1) with ipilimumab (CTLA-4) resulted in significant higher overall survival and response rates of patients with renal-cell carcinoma .
It was reported that combination of nivolumab with ipilimumab which are the medications for treating cancer is active in melanoma brain metastases and may be considered for the first-choice therapy .
Ferrari et al. expanded the therapy in the natural killer (NK) cell field where they designed the antibodies to inhibit tumor growth by stoping the shedding of cell surface MICA and MICB by human cancer cells which are recognized by NK cells to attack tumor cells .
Vonderheide commented that CD40 which is an receptor found on antigen presenting cell may play a critical role in increase the response rate in the immunotherapy . Porter et al. showed the Penn grading on the CAR T therapy . June et al. shared a review on CAR T cell immunotherapy .
Armand et al. confirmed the safety and efficacy of Nivolumab based on the study of an extended follow-up response of 205 treated patents .
Burnett et al. reported the importance of B cells and uncovered the ‘secret weapon’ of the immune system .
Eggermount et al. showed a “significant longer recurrence-free survival than placebo, with no new toxic effects identified” .
Szabados et al. found that ‘the activity of chemotherapy was maintained despite previous exposure to immune therapy” . Inherently, in another study, Tomasini et al. showed that durvalumab after chemoradiotherapy may also be a new treatment option .
Chester et al. showed the combination of PD1 and a tumor necrosis factor receptor 4-1BB expressed on T and NK Cells results in cytokine secretion and increase antibody-dependent cell mediated cytotoxicity is another promising immunotherapy .
Rossin et al. reported a non-internalising antibody-drug conjugates (ADCs) for drug release at a specific target site .
Qi et al.  reported their bi-specific antibodies (biAbs) battle tumors by targeting a membrane-proximal epitope of ROR1. The biAbs seems another promising strategy for cancer treatment, which has been growing rapidly in the last two years.
Imkeller et al. showed that the circumsporozoite protein of the malaria parasite plasmodium falciparum (PfCSP) could improve the B cell activation .
However, bad news on these treatments was also reported.
Moslehi et al.  used Vigibase to study the outcomes of the immune checkpoint inhibitor-based therapy (combination PD-1 and CTLA-4) and found 46 out of 101 treated patient were dead because of severe myocarditis, which casted a shadow over the immune based therapy.
Ratner et al.  reported that the unexpected treatment results of three patients with adult T-cell leukemia-lymphoma (ATLL). In all three cases, rapid progressions of the disease were observed after a single dose of nivolumab.
- Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, et al. (2018) Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med 378: 1277-1290.
- Long GV, Atkinson V, Lo S, Sandhu S, Guminski AD, et al. (2018) Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol 19: 672-681.
- Ferrari de Andrade L, Tay RE, Pan D, Luoma AM, Ito Y, et al. (2018) Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity. Science 359: 1537-1542.
- Vonderheide RH (2018) The Immune Revolution: A Case for Priming, Not Checkpoint. Cancer Cell 33: 563-569.
- Porter D, Frey N, Wood PA, Weng Y, Grupp SA, et al. (2018) Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel. J Hematol Oncol 11: 35.
- June CH, O'Connor RS, Kawalekar OU, Ghassemi S, Milone MC, et al. (2018) CAR T cell immunotherapy for human cancer. Science 359: 1361-1365.
- Armand P, Engert A, Younes A, Fanale M, Santoro A, et al. (2018) Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial. J Clin Oncol 36: 1428-1439.
- Burnett DL, Langley DB, Schofield P, Hermes JR, Chan TD, et al. (2018) Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination. Science 360: 223-226.
- Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson V, et al. (2018) Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. N Engl J Med 378: 1789-1801.
- Szabados B, van Dijk N, Tang YZ, van der Heijden MS, Wimalasingham A, et al. (2018) Response Rate to Chemotherapy After Immune Checkpoint Inhibition in Metastatic Urothelial Cancer. Eur Urol 73: 149-152.
- Tomasini P, Greillier L, Boyer A, Jeanson A, Barlesi F, et al. (2018) Durvalumab after chemoradiotherapy in stage III non-small cell lung cancer. J Thorac Dis (Suppl 9): S1032-S1036.
- Chester C, Sanmamed MF, Wang J, Melero I (2018) Immunotherapy targeting 4-1BB: mechanistic rationale, clinical results, and future strategies. Blood 131: 49-57.
- Rossin R, Versteegen RM, Wu J, Khasanov A, Wessels HJ, et al. (2018) Chemically triggered drug release from an antibody-drug conjugate leads to potent antitumour activity in mice. Nat Commun 9: 1484.
- Qi J, Li X, Peng H, Cook EM, Dadashian EL, et al. (2018) Potent and selective antitumor activity of a T cell-engaging bispecific antibody targeting a membrane-proximal epitope of ROR1. Proc Natl Acad Sci U S A 115: E5467-E5476.
- Imkeller K, Scally SW, Bosch A, Martí GP, Costa G, et al. (2018) Antihomotypic affinity maturation improves human B cell responses against a repetitive epitope. Science 360: 1358-1362.
- Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB, et al. (2018) Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet 391: 933.
- Ratner L, Waldmann TA, Janakiram M, Brammer JE (2018) Rapid Progression of Adult T-Cell Leukemia-Lymphoma after PD-1 Inhibitor Therapy. N Engl J Med 378: 1947-1948.
- FDA Alerts Health Care Professionals and Oncology Clinical Investigators about an Efficacy Issue Identified in Clinical Trials for Some Patients Taking Keytruda (pembrolizumab) or Tecentriq (atezolizumab) as Monotherapy to Treat Urothelial Cancer with Low Expression of PD-L1.
Citation: Feng HJ (2018) Recent Developments in Gene Therapy and Immunotherapy. J Nanomedine Biotherapeutic Discov 8: e149. DOI: 10.4172/2155-983X.1000e150
Copyright: © 2018 Ji HF. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
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