Immunotherapy: Timeline of key events

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This was first observed by Padmanee Sharma. Her findings provided an important pathway for improving the clinical efficacy of anti-CTLA-4 therapy. They were first published Chrysoula I Liakou, Ashish Kamat, Derek Ng Tang, Hong Chen, Jingjing Sun, Patricia Troncoso, Christopher Logothetis, and Padmanee Sharma, ‘CTLA-4 blockade increases IFNgamma-producing CD4+ICOShi T cells to shift the ratio of effector to regulatory T cells in cancer patients’, PNAS USA, 105/39 (Sept 2008), 14987-92.2006-01-01T00:00:00+0000Anti-cancer effect pinpointed to macrophages, natural killer cells and neutrophils. This was surprising because before this such white blood cells were assumed to only be effective against bacteria and fungal organisms. Now seen to provide immunity against cancer. A.M. Hicks, G. Redlinger, M.C. Willingham et al, 'Transferable anticancer innate immunity in spontaneous regression/complete resistance mice', PNAS, 103/20 (2006), 7753-58.2006-03-28T00:00:00+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+0000Results presented by Zheng Cui to third conference on 'Strategies for Engineered Negligible Senescence' held at Queen’s College Cambridge, UK.2007-09-20T00:00:00+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+0000More than 82 per cent of the patients went into remission. 2015-04-01T00:00:00+0000The drugs use a monoclonal antibody to block a protein known as PD-1, which functions as an immune checkpoint, being responsible for preventing the activation of T-cells. Promising results were presented to American Society for Clinical Conference from trials directed towards treating lung and skin cancer. 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+0000Research conducted by team led by immunologist Laurence Zitvogel. M. Vetizou et al, 'Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota', Science, 350/6264, (2015), 1079-84. doi: 10.1126/science.aad1329.2015-11-27T00:00:00+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+0000The trial was proposed by Carl June at University of Pennsylvannia to treat patients with multiple myeloma, melanoma and sarcoma. The study was approved by the US NIH Recombinant DNA Advisory Committee. It approved the use of CRISPR/Cas 9 to genetically modify immune cells to attack cancer in 18 patients. The trial was designed to test whether CRISPR is safe for use in humans. 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+0000Announcement based on study of 221 patients with metastatic melanoma, approximately half of whom were treated with a PD1 checkpoint inhibitor drug. The research was conducted by researchers led by Jennifer Wargo at the University of Texas MD Anderson Cancer Center. V. Gopalakrishnan et al, ASCO-SITC Clinical Immuno-Oncology Symposium. Abstract 02. Presented February 24, 2017. 2017-02-24T00:00:00+0000
Date Event People Places Sciences
2006Inducible co-stimulator (ICOS) protein found to enhance anti-CTLA-4 treatment in destruction of cancer cellsSharma, Liakou, Kamat, Ng Tang, Chen, Sun, Troncoso, LogothetisMD Anderson Cancer CenterCancer immunotherapy, Immune checkpoint inhibitors
28 Mar 2006Normal mice shown to become resistant to cancer when injected with white blood cells taken from mutant mice known to ward off aggressive cancer. Hicks, Redlinger, Willingham, Alexander-Miller, Kap-Herr, Pettenati, Sanders, Weir, Du, Kim, Simpson, Old, CuiWake Forest University, Ludwig Institute for Cancer ResearchOncology, Cancer Immunotherapy
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
20 Sep 2007Experiments in mice indicate cancer-killing capacity of granulocytes, white blood cells taken from humansCuiWake Forest UniversityCancer Immunotherapy, Oncology
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
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 Allison 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
27 Nov 2015Experiments in mice indicate that a tumour's response to cancer immunotherapy using CTLA-4 checkpoint inhibitor can be improved by changing the gut microbiome Zitvogel, Veitzou, Institut Gustave RoussyCancer immunotherapy, Immune checkpoint inhibitors, Oncology, Microbiome
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, Immune checkpoint inhibitors
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 20162016: NIH gives green light for first clinical trial using gene editing tool CRISPR/Cas 9 to treat patientsJuneUniversity of PennsylvaniaCRISPR-Cas9, Gene editing, Gene therapy, 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
24 Feb 2017Researchers report patients with greater diversity of gut bacteria have better response to cancer immunotherapyWargo, GopalakrishnanMD Anderson Cancer CenterCancer immunotherapy, Immune checkpoint inhibitors, Oncology, Microbiome

2006

Inducible co-stimulator (ICOS) protein found to enhance anti-CTLA-4 treatment in destruction of cancer cells

28 Mar 2006

Normal mice shown to become resistant to cancer when injected with white blood cells taken from mutant mice known to ward off aggressive 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

20 Sep 2007

Experiments in mice indicate cancer-killing capacity of granulocytes, white blood cells taken from humans

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

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

27 Nov 2015

Experiments in mice indicate that a tumour's response to cancer immunotherapy using CTLA-4 checkpoint inhibitor can be improved by changing the gut microbiome

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

2016: NIH gives green light for first clinical trial using gene editing tool CRISPR/Cas 9 to treat patients

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.

24 Feb 2017

Researchers report patients with greater diversity of gut bacteria have better response to cancer immunotherapy