Immunotherapy: Timeline of key events

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G Gross, T Waks, Z Eshhar, 'Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity (chimeric genes/antibody variable region)', Proc Natl Acad Sci USA, 86 (1989), 10024-8.1989-12-01T00:00:00+0000G. Gross, T. Waks, Z. Eshhar, 'Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity', PNAS USA, 86 (1989), 10024–8.1989-12-01T00:00:00+0000The approval was given based on results from a clinical trial carried out by Harry Herr and Herbert Oettgen. The BCG vaccine stimulates an immune response that targets both the tuberculosis bacteria and bladder cancer cells. 1990-01-01T00:00:00+0000A. 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+0000The work was led by Padmanee Sharma. The team's finding appeared in P. Sharma et al, ‘Thymus-leukaemia antigen interacts with T cells and self-peptides’, Journal Immunology, 156 (1996), 987-96.1996-02-01T00:00:00+0000DR Leach, MF Krummel, JP Allison, 'Enchancement of antitumor immunity by CTLA-4 blockade', Science, 271/5256 (1996), 1734-36. The discovery laid the foundation for the development immune checkpoint inhibitor drugs to unleash the immune system's destruction of cancer. 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+00002003-01-01T00:00:00+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+0000Z. Cui, M. C. Willingham, A. Hicks et al, 'Spontaneous regression of advanced cancer: Identification of a unique genetically determined, age-dependent trait in mice', PNAS, 100/11 (2003), 6682-7. 2003-03-19T00:00:00+0000Padmanee Sharma et al, ‘Frequency of NY-ESO-1 and LAGE-1 expression in bladder cancer and evidence of a new NY-ESO-1 T-cell epitope in a patient with bladder cancer’, Cancer Immunology, 3 (Dec 13 2003), 19.2003-12-13T00:00:00+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+0000
Date Event People Places Sciences
Dec 1989First use of genetically engineered T cells to redirect T cells to recognise and attack tumour cellsGross, Waks, EshharWeizmann InstituteGene therapy, Immunology, Cancer immunotherapy, Oncology
Dec 1989Concept of enhancing T cells using chimeric antigen receptors published for first timeGross, Waks, EshharWeizmann InstituteAdoptive cell therapy, Cancer immunotherapy, Gene therapy
1990US FDA approved BCG, a bacterial vaccine against tuberculosis, to treat early stage bladder cancer. It was the first FDA approved immunotherapyHerr, OettgenMemorial Sloan Kettering Cancer CenterImmunology, Cancer immunotherapy, Oncology, Virology, Vaccines
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
1 Feb 1996Paper published indicating thymus-leukaemia antigen, a cell-surface marker, stimulates T cells to destroy specific target cellsSharmaPennsylvania State UniversityCancer immunotherapy, Oncology
22 Mar 1996Mice experiments published demonstrating that blocking the CTLA-4 molecule on immune cells can cure cancerLeach, Krummel, AllisonUniversity of 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
1 Jan 2003Sharma received ASCO Young Investigator Award to carry out clinical trials with NY-ES0-1 cancer vaccineSharmaMemorial Sloan-Kettering Cancer CenterCancer 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
19 Mar 2003Mutant mouse discovered capable of warding off aggressive cancer and its offspring found to confer resistance to cancer in 40% of his offspringCui, Willingham, Hicks, Alexander-Miller, Howard, Hawkins, Millier, Weir, Du, DeLongWake Forest UniversityOncology, Cancer Immunotherapy
13 Dec 2003Sharma discovered some bladder cancer cells expressed the marker NY-ESO-1 providing means for cancer vaccineSharmaMemorial Sloan-Kettering Cancer CenterCancer immunotherapy, Oncology
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

Dec 1989

First use of genetically engineered T cells to redirect T cells to recognise and attack tumour cells

Dec 1989

Concept of enhancing T cells using chimeric antigen receptors published for first time

1990

US FDA approved BCG, a bacterial vaccine against tuberculosis, to treat early stage bladder cancer. It was the first FDA approved immunotherapy

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

1 Feb 1996

Paper published indicating thymus-leukaemia antigen, a cell-surface marker, stimulates T cells to destroy specific target 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

1 Jan 2003

Sharma received ASCO Young Investigator Award to carry out clinical trials with NY-ES0-1 cancer vaccine

2003

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

19 Mar 2003

Mutant mouse discovered capable of warding off aggressive cancer and its offspring found to confer resistance to cancer in 40% of his offspring

13 Dec 2003

Sharma discovered some bladder cancer cells expressed the marker NY-ESO-1 providing means for cancer vaccine

May 2005

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

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