Immunotherapy: Timeline of key events

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A. Kasid et al, 'Human gene transfer: characterization of human tumor-infiltrating lymphocytes as vehicles for retroviral-mediated gene transfer in man', PNAS USA, 87/1 (1990), 473-77.1990-01-01T00:00:00+0000S.A. Rosenberg et al, 'Gene Transfer into Humans — Immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction', NEJM, 323 (1990), 570-78.1990-08-30T00:00:00+0000Z Eshhar, 'Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors', PNAS USA, 90/2 (1989), 720-24.1993-01-15T00:00:00+0000G Dranoff, E Jaffee, A Lazenby, P Golumbek, H Levitsky, K Brose, V Jackson, H Hamada, D Pardoll, RC Mulligan, 'Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity', Proc Natl Acad Sci USA, 90 (1993), 3539–43.1993-04-15T00:00:00+0000A Bendelac et al, Science, 263 (1994), 1774-78; A Bendelac et al, Science, 268 (1995), 863-5. 1994-03-25T00:00:00+0000DR Leach, MF Krummel, JP Allison, 'Enchancement of antitumor immunity by CTLA-4 blockade', Science, 271/5256 (1996), 1734-36.1996-03-22T00:00:00+0000B 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 two companies agreed to share the costs and responsibilities of research and product development up to the completion of a Phase 2 clinical study in each party's territory.2005-05-01T00:00:00+0000R.A. Morgan et al, 'Cancer regression in patients after transfer of genetically engineered lymphocytes', Science. 2006;314:126–129.2006-10-06T00:00:00+0000M.H. Kershaw, et al, 'A Phase I Study on Adoptive Immunotherapy Using Gene-Modified T Cells for Ovarian Cancer', Clinical Cancer Research, 11/20 (2006), 6106-15.2006-10-15T00:00:00+0000Drug, MSX-1106, to be assessed for malignant melanoma, renal cell cancer, castrate-resistant prostate cancer and non-small cell lung carcinoma2008-11-24T00:00:00+0000J.N. Kochenderfer,et al, Blood, 116/20 (2010); M. Kalos, et al, Sci Tranl Med, 5 (2013), 95ra73; R.J. Brentijens et al, Science Translational Medicine, 5/177 (2013), 177ra882010-01-01T00:00:00+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+0000
Date Event People Places Sciences
Jan 1990Gene therapy concept proven in first human trialsKasid, Morecki, Aebersold, Cornetta, Culver, Freeman, Director, Lotze, Blaese, AndersonNational Cancer InstituteAdoptive cell therapy, Cancer immunotherapy, Gene therapy
30 Aug 1990Treatment with gene modified tumour-infiltrating lymphocytes shown to be promising immunotherapy for patients with advance melanomaRosenberg, Aebersold, Cornetta, Kasid, Morgan, Moen, Karson, Lotze, Yang, Topalian, Merino, Culver, Miller, Blaese, AndersonNational Cancer InstituteAdoptive cell therapy, Cancer immunotherapy, Gene therapy
15 Jan 1993Chimeric receptor genes added to T lymphocytes shown to enhance power of adoptive cellular therapy against tumoursEshhar, Waks, Gross, SchindlerWeizmann InstituteAdoptive cell therapy, Cancer immunotherapy, Gene therapy
15 Apr 1993Immune molecule, granulocyte-macrophage colony stimulating factor or GM-CSF, discovered to strengthen immunity against tumours Dranoff, Jaffee, Lazenby, Golumbek, Levitsky, Brose, Jackson, Hamada, Pardoll, MulliganMassachusetts Institute of TechnologyImmunology, Cancer immunotherapy, Oncology
1994 - 1995Identification and characterisation of the natural killer T cell, a lymphocyte able to bind and kill certain tumour and virus-infected cellsBendelacUniversity of ChicagoImmunology, Cancer immunotherapy, Oncology
22 Mar 1996Mice experiments published demonstrating that blocking the CTLA-4 molecule on immune cells can cure cancerLeach, Krummel, AllisonUniversity California BerkeleyImmune checkpoint inhibitors, Immunology, Cancer immunotherapy, Oncology
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
May 2005Medarex and Ono Pharmaceuticals entered research alliance to develop a fully human anti-PD-1 antibody for the treatment of cancer Medarex, Ono PharmaceuticalImmune checkpoint inhibitors, Immunotherapy, Monoclonal antibodies
6 Oct 2006Genetically engineered lymphocytes shown to be promising cancer treatmentMorgan, Dudley, Wunderlich, Hughes, Yang, Sherry, Royal, Topalian, Kammula, Restifo, Zheng, Nahvi Vries, Rogers-Freezer, Mavroukakis, RosenbergNational Cancer InstituteAdoptive cell therapy, Cancer immunotherapy, Gene therapy
15 Oct 2006Adoptive cellular therapy using chimeric antigen receptor T cells shown to be safe in small group of patients with ovarian cancerKershaw, Westwood, Parker, Wang, Eshhar, Mavroukakis, White, Wunderlich, Canevari, Rogers-Freezer, Chen, Yang, Rosenberg, HwuNational Cancer Institute, University of Melbourne, M.D. Anderson Cancer Center, Weizmann Institute, Istituto Nazionale TumoriAdoptive cell therapy, Cancer immunotherapy, Gene therapy
24 Nov 2008First anti-PD-1 antibody entered phase 1 clinical trial for cancer Medarex, Ono PharmaceuticalImmune checkpoint inhibitors, Immunotherapy, Monoclonal antibodies
2010 - 2013Studies show CD19-specific CAR-modified T cells to be promising treatment in patients with B cell malignanciesKochenderfer, Kalos, BrentjensNational Cancer Institute, National Institutes of Health, Memorial Sloan-Kettering Cancer Center, University of PennsylvaniaAdoptive cell therapy, Cancer immunotherapy, Gene therapy
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 Honko, Freeman, LonbergMedarex, Bristol-Myers Squibb, Ono PharmaceuticalImmune checkpoint inhibitors, Cancer immunotherapy, Oncology, Monoclonal antibodies

Jan 1990

Gene therapy concept proven in first human trials

30 Aug 1990

Treatment with gene modified tumour-infiltrating lymphocytes shown to be promising immunotherapy for patients with advance melanoma

15 Jan 1993

Chimeric receptor genes added to T lymphocytes shown to enhance power of adoptive cellular therapy against tumours

15 Apr 1993

Immune molecule, granulocyte-macrophage colony stimulating factor or GM-CSF, discovered to strengthen immunity against tumours

1994 - 1995

Identification and characterisation of the natural killer T cell, a lymphocyte able to bind and kill certain tumour and virus-infected cells

22 Mar 1996

Mice experiments published demonstrating that blocking the CTLA-4 molecule on immune cells can cure cancer

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

May 2005

Medarex and Ono Pharmaceuticals entered research alliance to develop a fully human anti-PD-1 antibody for the treatment of cancer

6 Oct 2006

Genetically engineered lymphocytes shown to be promising cancer treatment

15 Oct 2006

Adoptive cellular therapy using chimeric antigen receptor T cells shown to be safe in small group of patients with ovarian cancer

24 Nov 2008

First anti-PD-1 antibody entered phase 1 clinical trial for cancer

2010 - 2013

Studies show CD19-specific CAR-modified T cells to be promising treatment in patients with B cell malignancies

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