Immunotherapy: Timeline of key events

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PJ Maddon et al, Cell, 42 (1985), 93-104; Littman et al, Cell, 40 (1985), 237-46. 1985-01-01T00:00:00+0000SA Rosenberg et al, 'Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer', New England Journal of Medicine, 313 (1985), 1485-92.1985-12-05T00:00:00+0000S.A. Rosenberg, P. Spiess, R. Lafreniere, 'A New Approach to the Adoptive Immunotherapy of Cancer with Tumor-Infiltrating Lymphocytes', Science, 233/4770 (1996), 1318-21.1986-09-19T00:00:00+0000MT Lotze, AE Chang, CA Seipp, C Simpson, JT Vetto, AS Rosenberg, 'High-dose recombinant interleukin 2 in the treatment of patients with disseminated cancer', JAMA, 256 (1986), 3117-24. 1986-12-12T00:00:00+0000The research was led by Thierry Boon and Etienne De Plaen at the Ludwig Institute for Cancer Research, Belgium1987-01-01T00:00:00+0000The clones were isolated from the blood of melanoma patient with long-term remission following vaccination with irradiated mutagenized autologous tumor cells. M Hein et al, 'Production of stable cytolytic T-cell clones directed against autologous human melanoma', International Journal of Cancer, 39 (1987), 390-96. 1987-03-15T00:00:00+0000Z Dembi et al, 'Transfection of the CD8 gene enhances T-cell recognition', Nature, 326 (1987), 510-11.1987-04-02T00:00:00+0000SA Rosenberg et al, 'A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone', New England Journal of Medicine, 9/316 (1987), 889-97. 1987-04-09T00:00:00+0000JF Brunet et al, 'A new member of the immunoglobulin superfamily--CTLA-4', Nature 328 (1987), 267-70. 1987-07-16T00:00:00+0000C Doyle, JL Strominger, 'Interaction between CD4 and class II MHC molecules mediates cell adhesion', Nature, 330 (1987), 256-9.1987-11-19T00:00:00+0000G Degiovanni et al, European Journal Immunology, 18 (1988+), 671-6; Knuth et al, Proc Natl Acad Sci USA, 86 (1989), 2804-08; Van den Eynde et al, International Journal of Cancer, 15 /44 (1989), 634-40. 1988-05-01T00:00:00+0000CE Rudd, JM Trevillyan, JD Dasgupta, LL Wong, SF Schlossman, 'The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (Pp58) from human T lymphocytes', Proc Natl Acad Sci USA, 85 (1988), 5190-94.1988-07-01T00:00:00+00001988-07-14T00:00:00+0000P Dariavach, MG Mattei, P Golstein, MP Lefranc, 'Human Ig superfamily CTLA-4 gene: chromosomal localization and identity of protein sequence between murine and human CTLA-4 cytoplasmic domains', European Journal Immunology, 18 (1988), 1901-05.1988-12-01T00:00:00+0000SA Rosenberg et al, 'Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report', New England Journal of Medicine, 319 (1988), 1676-80.1988-12-22T00:00:00+0000CV Thompson, T Lindsten, JA Ledbetter, SL Kunkel, SA Young, SG Emerson, JM Leiden, CL June, 'CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines', Proc Natl Acad Sci U S A , 86 (1989),1333-7.1989-02-01T00:00:00+0000Study conducted by French Anderson in collaboration with Steven Rosenberg in 52 year old cancer patient as preliminary experiment to test gene therapy in children with severe combined immunodeficiency disorder. 1989-05-01T00:00:00+0000M Kobayashi, L Fitz, M Ryan, RM Hewick, SC Clark, S Chan, R Loudon, F Sherman, B Perussia, G Trinchieri, ' Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes', Journal Expermental Medicine', 170 (1989), 827-45.1989-09-01T00:00:00+0000G 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+0000
Date Event People Places Sciences
1985T cell surface proteins CD4 and CD8 cloned Maddon, Littman, Godfrey, Maddon Chess, AxelColumbia UniversityImmunology, Cancer immunotherapy, Oncology
Dec 1985IL-2 based immunotherapy shown to reduce tumours in patients with melanoma and renal cell cancerRosenbergNational Cancer InstituteImmunology, Cancer immunotherapy, Oncology, Adoptive cell therapy
19 Sep 1986Adoptive transfer of tumor-infiltrating lymphocytes shown in mice to be 50 to 100 times more effective in therapeutic potency than lymphokine-activated killer cellsRosenberg, Spiess, LafrieniereNational Cancer InstituteAdoptive cell therapy, Cancer immunotherapy, Gene theray
Dec 1986Anti-tumour responses observed in 3 out of 10 patients given high-doses of Interleukin-2 (IL-2) Rosenberg, Lotze, Chang, Seipp, Simpson, VettoNational Cancer InstituteImmunology, Cancer immunotherapy, Oncology, Adoptive cell therapy
1987 - 1989Scientists lay the foundation for the cloning of human tumour antigens recognised by cytotoxic T lymphocytes, a type of white blood cell that kills cancer cellsDe Plaen, BoonLudwig Institute for Cancer ResearchImmunology, Cancer immunotherapy, Oncology
15 Mar 1987First stable human anti-tumour cytotoxic T cell clones isolated and maintained in cultureHerin, Lemoine, Weynants, Vessiere, Van Pel, Knuth, Devos, BoonLudwig InstituteImmunology, Cancer immunotherapy, Oncology
Apr 1987CD8 coreceptor proven to be actively involved in antigen recognition by killer T cellsDembic, Haas, Zamoyska, Parnes, Steinmetz, von BoehmerBasel Institute of ImmunologyImmunology, Cancer immunotherapy, Oncology
9 Apr 1987Successful results reported for trial using the cytokine IL-2 and lymphokine-activated killer cells to treat cancerRosenbergNational Cancer InstituteCancer immunotherapy, Adoptive cell therapy
Jul 1987Identification of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)Brunet, Denizot, Luciani, Roux-Dosseto, Suzan, Mattei, GolsteinINSERM-CNRSImmune checkpoint inhibitors, Immunology, Cancer immunotherapy, Oncology
Nov 1987First evidence provided for the interaction between the surface molecule CD4 and major histocompatibility class IIDoyle, StromingerHarvard UniversityImmunology, Cancer immunotherapy, Oncology
May 1988 - Oct 1989Cytotoxic T lymphocytes shown to recognise distinct surface markers on human melanomaWolfel, Knuth, Degiovanni, Van den Eynde, Hainaut, BoonLudwig Institute for Cancer ResearchImmunology, Cancer immunotherapy, Oncology
Jul 1988Biochemical initiators of T Cell activitation, CD4 and CD8-p56, discoveredRudd, Trevillyan, Dasupta, Wong, SchlossmanDana-Faber Cancer Institute, Harvard University, Tech UniversityImmunology, Cancer immunotherapy, Oncology
1988 - 1989First evidence discovered of a physical link between oncoproteins and tumour suppressors  Immunology, Cancer immunotherapy, Oncology
Dec 1988Scientists report cloning the gene for the human cytotoxic T lymphocyte-associated antigen (CTLA-4)Dariavach, Mattei, Golstein, LefrancINSERM-CNRSImmune checkpoint inhibitors, Immunology, Cancer immunotherapy, Oncology
22 Dec 19889 out of 15 melanoma patients successfully treated with autologous tumor-infiltrating lymphocytes cultured with the cytokine IL-2RosenbergNational Cancer InstituteCancer immunotherapy, Adoptive cell therapy
Feb 1989Scientists demonstrate the importance of CD28, a cell surface molecule found on T-cells, for the activation and survival of T cellsThompson, Lindsten, Ledbetter, Kunkel, Young, Emerson, Leiden, JuneHoward Hughes Medical InstituteImmunology, Cancer immunotherapy, Oncology
May 1989First human test demonstrated safety of retroviral vector for gene therapy and potential of laboratory produced tumor killing cells for cancer immunotherapyAnderson, RosenbergNational Institutes of HealthAdoptive cell therapy, Cancer immunotherapy, Gene therapy
Sep 1989Giorgio Trinchieri and colleagues identified interleukin-12 (IL-12), a cytokine that helps regulate the body’s resistance to infections and cancerKobayashi, Fitz, Ryan, Hewick, Clark, Chan, Loudon, Sherman, Perussia, TrinchieriWistar InstituteImmunology, Cancer immunotherapy, Oncology
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

1985

T cell surface proteins CD4 and CD8 cloned

Dec 1985

IL-2 based immunotherapy shown to reduce tumours in patients with melanoma and renal cell cancer

19 Sep 1986

Adoptive transfer of tumor-infiltrating lymphocytes shown in mice to be 50 to 100 times more effective in therapeutic potency than lymphokine-activated killer cells

Dec 1986

Anti-tumour responses observed in 3 out of 10 patients given high-doses of Interleukin-2 (IL-2)

1987 - 1989

Scientists lay the foundation for the cloning of human tumour antigens recognised by cytotoxic T lymphocytes, a type of white blood cell that kills cancer cells

15 Mar 1987

First stable human anti-tumour cytotoxic T cell clones isolated and maintained in culture

Apr 1987

CD8 coreceptor proven to be actively involved in antigen recognition by killer T cells

9 Apr 1987

Successful results reported for trial using the cytokine IL-2 and lymphokine-activated killer cells to treat cancer

Jul 1987

Identification of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)

Nov 1987

First evidence provided for the interaction between the surface molecule CD4 and major histocompatibility class II

May 1988 - Oct 1989

Cytotoxic T lymphocytes shown to recognise distinct surface markers on human melanoma

Jul 1988

Biochemical initiators of T Cell activitation, CD4 and CD8-p56, discovered

1988 - 1989

First evidence discovered of a physical link between oncoproteins and tumour suppressors

Dec 1988

Scientists report cloning the gene for the human cytotoxic T lymphocyte-associated antigen (CTLA-4)

22 Dec 1988

9 out of 15 melanoma patients successfully treated with autologous tumor-infiltrating lymphocytes cultured with the cytokine IL-2

Feb 1989

Scientists demonstrate the importance of CD28, a cell surface molecule found on T-cells, for the activation and survival of T cells

May 1989

First human test demonstrated safety of retroviral vector for gene therapy and potential of laboratory produced tumor killing cells for cancer immunotherapy

Sep 1989

Giorgio Trinchieri and colleagues identified interleukin-12 (IL-12), a cytokine that helps regulate the body’s resistance to infections and cancer

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