Immunotherapy: Timeline of key events

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B Bogen, 'Peripheral T cell tolerance as a tumor escape mechanism', European Journal Immunology, 26 (1996), 2671-79.1996-11-01T00:00:00+0000Ritxuan (rituiximab) is approved for the treatment of non-Hodgkin Lymphoma. The drug arose out of Ronald Levy's research for three decades to find a way of harnessing the power of the body's own immune system to fight cancer. 1997-01-01T00:00:00+0000Launched by the biotechnology company Medarex in collaboration with Jim Allison. 2000-01-01T00:00:00+0000Research led by Rajasekharan Somasundaram and Dorothee Herlyn published in Cancer Research.2002-09-14T00:00:00+0000Y. Iwai, M. Ishida, Y. Tanaka, T. Okazaki, T. Honjo, N. Minato, 'Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade', PNAS USA, 99/19 (2002), 12293-7.2002-09-17T00:00:00+0000JD Fontenot, MA Gavin, AY Rudensky, 'Foxp3 programs the development and function of CD4+CD25+ regulatory T cells', Nature Immunology, 4 (2003), 330-36.2003-03-03T00:00:00+0000The drug was approved for the treatment of unresectable or metastatic melanoma. The drug uses a monoclonal that blocks CTLA-4 so as to activate an immune response against the cancer.2011-03-25T00:00:00+0000Emily Whitehead, aged 6, was the first child ever to be given the genetically altered T cells. She experienced severe side effects, including raging fever, dramatic drop in blood pressure, lung congestion, but emerged cancer free. Treatment was led by Carl June. Engineering the T cells was estimated to cost $20,000 per patient. 2012-04-01T00:00:00+0000The drug, a monoclonal antibody, was approved by the FDA for the treatment of patients with melanoma. 2014-12-22T00:00:00+0000More than 82 per cent of the patients went into remission. 2015-04-01T00:00:00+0000Results presented to American Society for Clinical Conference from trials involving monoclonal antibody drugs for lung and skin cancer. The drugs block a protein known as PD-1, which functions as an immune checkpoint, being responsible for preventing the activation of T-cells.2015-06-05T00:00:00+0000K.B. Chiappinelli, P.L. Strissel, A. Desrichard, et al, 'Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses', Cell, 162 (2015), 974-86.2015-08-27T00:00:00+0000Based on the analysis of data from hundreds of patients, scientists found markers on tumour cells flagging up very early mutations of the disease. The advantage is these appear on all tumour cells, thereby providing a good target for treatment. N. McGranahan, et al, 'Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade', Science, 351/6280 (2016), 1463-69. 2016-03-25T00:00:00+0000UK scientists show how the TALENs gene editing tool can be used to switch on the immune system to stop cancer. L. Menger, et al, 'TALEN-Mediated Inactivation of PD-1 in Tumor-Reactive Lymphocytes Promotes Intratumoral T-cell Persistence and Rejection of Established Tumors', Cancer Research, 2016, doi: 10.1158/0008-5472.CAN-15-3352. 2016-04-15T00:00:00+0000Work led by Carl June at University of Pennsylvannia to treat patients with multiple myeloma, melanoma and sarcoma.2016-06-21T00:00:00+0000Research carried out by a team led by Dimitry I Gabriolvich. 2016-08-05T00:00:00+0000It was the first time tyhe FDA approved an immune checkpoint inhibitor for the treatment of lung cancer. The drug was developed by Merck & Co.2016-10-24T00:00:00+0000Developed by EMD Serono avelumab is a PD-L1 blocking monoclonal antibody. It was the first FDA approved product to treat metastatic Merckel cell carcinoma.2017-03-23T00:00:00+0000The drug CTL019 (tisagenlecleucel) was developed by Novartis. Treatment involves removing T cells from the patient and genetically modifying them to increase their capacity to bind to tumour cells in order to get the immune sytem to attack the tumours. It is targeted at children and young adults from three to 25 years old who have not responded to traditional treatments.2017-07-12T00:00:00+0000
Date Event People Places Sciences
Nov 1996Experiments demostrate antigen-specific CD4+ and T cells become tolerant during tumour growth in test tubes  Immunology, Cancer immunotherapy, Oncology
1997FDA approved the first monoclonal antibody cancer drug for the American marketLevy, RastetterStanford University Medical School, Idec PharmaceuticalsCancer immunotherapy, Monoclonal antibodies
2000First clinical trials launched to test first immune checkpoint inhibitor drug containing a monoclonal antibody against CTLA-4 (ipilimumab, Yervoy®)AllisonMedarex, University of California BerkleyImmune checkpoint inhibitors, Immunology, Cancer immunotherapy, Oncology, Monoclonal antibodies
14 Sep 2002Regulatory T cells discovered to restrain cytolytic T cells attacking cancer via messanger chemical called TGF-betaHerlyn, SomasundaramWistar InstituteImmunology, Cancer immunotherapy, Oncology
17 Sep 2002Cancer cells shown to be capable of hijacking PD-1 protein to evade destruction by immune systemIwai , Ishida, Tanaka, Okazaki, Honjo, MinatoJapan Science and Technology CorporationImmune checkpoint inhibitors, Cancer immunotherapy, Oncology
2003Genetic switch identified that controls the development of T cells, an important immune cell that controls against autoimmunity and excess inflammationFontenot, Gavin, RudenskyHoward Hughes Medical Institute, University of WashingtonImmunology, Cancer immunotherapy
25 Mar 2011First immune checkpoint inhibitor drug targeting CTLA4 (ipilimumab, Yervoy®), approved by the FDAAllisonMedarex, University of California BerkleyImmune checkpoint inhibitors, Cancer immunotherapy, Oncology, Monoclonal antibodies
Apr 2012First child with leukaemia treated with adoptive cell therapy (CAR-T therapy)June, WhiteheadChildren's Hospital of Philadelphia, University of PennsylvaniaCancer immunotherapy, Oncology, Adoptive cell therapy
22 Dec 2014First immune checkpoint inhibitor drug targeting PD-1 (nivolumab, Opdivo®) approved in US AllisonMedarex, Bristol-Myers Squibb, University of California BerkleyImmune checkpoint inhibitors, Cancer immunotherapy, Oncology, Monoclonal antibodies
Apr 2015 - Aug 2016Adoptive cell therapy (CAR-T therapy) trial conducted with 63 leukaemia patients in 11 countriesJuneNovartisCancer immunotherapy, Onoclogy, Adoptive cell therapy
5 Jun 2015Two immunotherapy drugs reported to stop cancer cells avoiding destruction by immune system   Cancer immunotherapy, Oncology, Monoclonal antibodies
27 Aug 2015Experiments with mice showed that azacytidine treatment enhanced the responsiveness of tumors to anti–CTLA-4 therapy  Cancer immunotherapy, Epigenetics, Immune checkpoint inhibitors, Oncology
25 Mar 2016Common tags discovered on the surface of cancer cells opening up new avenues for immunotherapyMcGranahan, Furness, Rosenthal, Ramskov, Lyngaa, Saini, Jamal-Hanjani, Wilson, Birkbak, Hiley, Watkins, Shafi, Murugaesu, Mitter, Akarca, Linares, Marafioti, Henry, Van Allen, Miao, Schilling, Schadendorf, Garraway, Makarov, Rizvi,m Snyder, Hellman, MerghUniversity College London, Cancer Research UK, Francis Crick Insitute, Dana-Farber Cancer Institute, Broad Institute, University Duisburg-Essen, Memorial Sloan Kettering Cancer Center, Columbia Univertsity, Weill Cornell Medical College, Harvard Medical SImmunology, Cancer immunotherapy, Oncology
15 Apr 2016Gene editing used to prompt immune cells to combat cancerQuezada, Johnson, Menger, Sledzinska, Bergerhoff, Vargas, Smith, Poirot, Pule, Hererro, PeggsUniversity College London, Cancer Research UK, CellectisImmunology, Oncology, TALENs, Gene editing, Cancer immunotherapy
21 Jun 2016US NIH Recombinant DNA Advisory Committee approved first study in 15 patients using CRISPR/Cas 9 to genetically modify immune cells to attack cancerJuneUniversity of PennsylvaniaCRISPR-Cas9, Gene editing, Gene Cancer immunotherapy
Aug 2016Marker identified for myeloid-derived suppressor cells, a type of cell associated with tumour resistance to certain cancer treatments Wistar InstituteImmunology, Cancer immunotherapy, Oncology
24 Oct 2016FDA approved pembrolizumab (Keytruda®) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test. MerckImmune checkpoint inhibitors, Cancer immunotherapy, Oncology, Monoclonal antibodies
23 Mar 2017US FDA granted accelerated approval to avelumab for the treatment of patients 12 years and older with metastatic Merkel cell carcinomaEMD SeronoImmune checkpoint inhibitors, Cancer immunotherapy, Oncology, Monoclonal antibodies
12 Jul 2017US FDA Oncologic Drugs Advisory Committee recommended the approval of the first adoptive cell therapy (CAR-T cell therapy) for B cell acute leukaemia Novartis, University of PennsylvaniaCancer immunotherapy, Oncology, Adoptive cell therapy

Nov 1996

Experiments demostrate antigen-specific CD4+ and T cells become tolerant during tumour growth in test tubes

1997

FDA approved the first monoclonal antibody cancer drug for the American market

2000

First clinical trials launched to test first immune checkpoint inhibitor drug containing a monoclonal antibody against CTLA-4 (ipilimumab, Yervoy®)

14 Sep 2002

Regulatory T cells discovered to restrain cytolytic T cells attacking cancer via messanger chemical called TGF-beta

17 Sep 2002

Cancer cells shown to be capable of hijacking PD-1 protein to evade destruction by immune system

2003

Genetic switch identified that controls the development of T cells, an important immune cell that controls against autoimmunity and excess inflammation

25 Mar 2011

First immune checkpoint inhibitor drug targeting CTLA4 (ipilimumab, Yervoy®), approved by the FDA

Apr 2012

First child with leukaemia treated with adoptive cell therapy (CAR-T therapy)

22 Dec 2014

First immune checkpoint inhibitor drug targeting PD-1 (nivolumab, Opdivo®) approved in US

Apr 2015 - Aug 2016

Adoptive cell therapy (CAR-T therapy) trial conducted with 63 leukaemia patients in 11 countries

5 Jun 2015

Two immunotherapy drugs reported to stop cancer cells avoiding destruction by immune system

27 Aug 2015

Experiments with mice showed that azacytidine treatment enhanced the responsiveness of tumors to anti–CTLA-4 therapy

25 Mar 2016

Common tags discovered on the surface of cancer cells opening up new avenues for immunotherapy

15 Apr 2016

Gene editing used to prompt immune cells to combat cancer

21 Jun 2016

US NIH Recombinant DNA Advisory Committee approved first study in 15 patients using CRISPR/Cas 9 to genetically modify immune cells to attack cancer

Aug 2016

Marker identified for myeloid-derived suppressor cells, a type of cell associated with tumour resistance to certain cancer treatments

24 Oct 2016

FDA approved pembrolizumab (Keytruda®) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test.

23 Mar 2017

US FDA granted accelerated approval to avelumab for the treatment of patients 12 years and older with metastatic Merkel cell carcinoma

12 Jul 2017

US FDA Oncologic Drugs Advisory Committee recommended the approval of the first adoptive cell therapy (CAR-T cell therapy) for B cell acute leukaemia