Immunotherapy: Timeline of key events

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Based on the observation that some tumours shrink in patients with a bacterial skin infection, the surgeon William Coley treated a 21 year old man with inoperable sarcoma with mixture containing heat-treated bacteria. The man went into complete remision. W. Coley, 'The Treatment of Malignant Tumors By Repeated Inoculations of Erysipelas: With A Report of Ten Original Cases', The American Journal of Medical Sciences, 105 (1893): 487-511. 1893-05-01T00:00:00+0000Antiserum preparted against human oesteogenic sarcoma in an ass and 2 dogs. Reported successful in treating 50 patients suffering from cancer of the stomach and chest wall. J Hericourt, C Richet, 'Traitement d'un cas de sarcome par la sarcome par la serotherapie', Seances Acad Sci, 120 (1895), 948-50.1895-01-01T00:00:00+0000The vaccine was developed by William Coley, a New York surgeon, together with the pharmaceutical company Parke, Davis & Co. The vaccine contained a combination of heat-killed bacteria. 1899-01-01T00:00:00+0000The work was carried out independently by Leo Loeb, in Canada and the US, and by Carl Jensen in Copenhagen. Results from the experiments showed some animals were more susceptible to transplanted tumour tissue than others. This ignited a debate 1901-01-01T00:00:00+0000Patients reported an alleviation of their symptoms. E von Leyden, F Blumenthal, 'Vorlaufige Mittheilungen uber einige Ergebnisse der Krebsforschung aug der I. medizinischen Klinik', Deutsche Med Wschr, 28 (1902), 637-8.1902-01-01T00:00:00+0000P Ehrlich, 'About the current state of carcinoma research', Lecture given to students at Amsterdam University, Association of Scientific work, 19081908-01-01T00:00:00+0000E. Freund, G. Kaminer, 'Ueber die Beziehungen zwischen Tumorzellen und Blutserum', Biochem. Ztschr, 26 (1910) 26, 312-24.1910-01-01T00:00:00+0000 JB Murphy, 'Studies on tissue specificity', Journal of Experimental Medicine, 19 (1914), 181-86.1914-01-01T00:00:00+0000The experiments involved increasing the number of lymphocytes in the blood of mice by treating them with low doses of X-rays. JB Murphy, JJ Morton, 'The effects of X-rays on the resistance to cancer in mice', Science, 42 (1915), 842. 1915-01-01T00:00:00+0000The trials were carried out by James B Murphy and colleagues at the Rockefeller Institute. 1916-01-01T00:00:00+0000E. Freund, G. Kaminer, Wiener Klinische Wochenschrift, Jan 19241924-01-01T00:00:00+0000E Witebsky, 'Disponibilitiit und Spezifitat alkoholloslicher Strukturen von Organen und bosartigen Geschwulsten', Zeitschrift fur Imrnunitaetsforschung, Allergie und Klinische Immunologie' 62 (1929), 35-73. 1929-01-01T00:00:00+0000R Pearl, 'Cancer and tuberculosis', American Journal of Hygiene, 9 (1929), 97-149. 1929-04-01T00:00:00+0000Lewis Thomas and Frank MacFarlane Burnet develop a theory that the immune system regularly screens and protects the body against cancer, and that cancer only develops when this mechanism fails. 1957-01-01T00:00:00+0000LJ Old, DA Clarke, B Benacerraf, 'Effect of bacillus calmette-guerin infection on transplanted tumours in the mouse', Nature, 184 (1959), 291-92.1959-07-25T00:00:00+0000LJ Old, EA Boyse, E Oettgen, ED Harven, ED Geering, B Williamson, P Clifford, 'Precipitating antibody in human serum to an antigen present in cultured Burkitt's lymphoma cells', Proc Natl Acad Sci USA, 56 (1966), 1699–1704.1966-12-01T00:00:00+0000I. Hellstrom, K. E. Hellstrom, C. A. Evans, G. Heppaer, G. E. Piece, I. P. S. Yang, 'Serum-mediated protection of neoplastic cells from inhibition by lymphocytes immune to their tumor-specific antigens', PNAS USA, 1969, 62, 362-9.1969-02-01T00:00:00+0000H. O. Sjogren, I. Hellstrom, S. C. Bansal, K. E. Hellstom, 'Suggestive evidence that the blocking antibodies of tumor-bearing individuals may be antigen--antibody complexes', PNAS, USA, 1971, 68/6, 1372-5. 1971-06-01T00:00:00+00001972-01-01T00:00:00+0000The transplant was carried out by Richard O'Reilly and Robert Good. This lays the foundation for the routine use of bone marrow transplants for treating some blood cancers. Such transplants are classed as immunotherapy because immune cells from the donor kill cancer cells in the recipient. 1973-01-01T00:00:00+0000
Date Event People Places Sciences
May 1893First successful treatment of cancer patient with immunotherapyColeyMemorial Sloan Kettering Cancer CenterCancer immunotherapy, Oncology
1895Humans treated with antiserum prepared against human cancer. This established the principle of using serotherapy to fight cancerHericourt, RichetCollege de FranceImmunology, Cancer immunotherapy, Oncology, Monoclonal antibodies
1899First commercial vaccine developed for treatment of sarcomaColeyMemorial Sloan Kettering Cancer Center, Parke Davis & CoImmunology, Cancer immunotherapy, Oncology,
1901 - 1903First successful transplants of tumours in animals reported, providing a new experimental system for studying the role of the immune system in cancerLeob, JensenUniversity of Pennsylvania, Agriculture and Veterinary InstituteCancer immunotherapy, Oncology
1902First attempt to vaccinate against cancer with a patient's own tumour tissuevon Leyden, Blumenthal Immunology, Cancer immunotherapy, Oncology
1908Paul Ehrlich reports that spontaneously developed tumours can be suppressed by the immune system EhrlichGoettingen UniversityCancer immunotherapy
1910Austrian physicians Ernest Freund and Gisa Kaminer observed that something in blood serum from cancer patients pervents the destruction of cancer cellsFreund, KaminerRudolf-Stiftung HospitalImmune checkpoint inhibitors, Cancer immunotherapy, Oncology
1914Experiments by James B Murphy demonstrate that lymphocytes help animals reject grafted tumoursMurphyRockefeller IntituteImmunology, Cancer immunotherapy, Oncology
1915 James B Murphy puts forward hypothesis that the nonspecific stimulation of lymphocytes could provide a cure for cancer based on experiments he and John J Morton carried out on miceMurphy, MortonRockefeller InstituteImmunology, Cancer immunotherapy, Oncology
1916 - 1922Disappointing results reported from clinical trials treating breast cancer patients with low doses of X-ray radiation following tumour removal, discrediting the theory that stimulation of lymphocytes could help cure cancer. MurphyRockefeller InstituteImmunology, Cancer immunotherapy, Oncology
1924Austrian physicians Ernest Freund and Gisa Kaminer discover a substance in intestines of cancer patients that reduce ability of normal serum to dissolve cancer cells. Freund, KaminerRudolf-Stiftung HospitalImmune checkpoint inhibitors, Cancer immunotherapy, Oncology
1929First molecular marker, antigen, identified on a tumour, laying foundation for use of antibodies to diagnose and treat cancerWitebsky University of HeidelbergImmunology, Cancer immunotherapy, Oncology, Monoclonal antibodies
Apr 1929Autopsies carried out on tuberculosis patients show them less likely to have contracted cancerPearlJohns Hopkins UniversityImmunology, Cancer immunotherapy, Oncology,
1957 - 1959Concept developed that the immune system naturally protects against cancerBurnet, Lewis Cancer immunotherapy, Oncology
25 Jul 1959Mice injected with BCG vaccine shown to develop resistance to growth of implanted tumours. This was the first direct evidence of the immune system's ability to prevent cancer. Old, Clarke, BenacerrafMemorial Sloan Kettering Cancer CenterCancer immunotherapy, Oncology
Dec 1966Scientists detect antibodies to the Epstein-Barr virus in patients with nasopharyngeal cancer which suggest the cancer is caused by a virus. Old, Boyse, OettgenMemorial Sloan Kettering Cancer CenterCancer immunotherapy, Oncology, Virology
Feb 1969Team led by Karl and Ingegerd Hellstrom observe serum from mice with chemically induced tumours can block reaction of lymphocytesHellstrom, Evans, Heppner, Pierce, Yang Fred Hutchinson Cancer CenterImmune checkpoint inhibitors, Cancer immunotherapy, Oncology
Jun 1971Hellstom team suggest that antibodies bound to tumour cells mask their detection by the immune system Sjogren, Hellstrom, BansalFred Hutchinson Cancer CenterImmune checkpoint inhibitors, Cancer immunotherapy, Oncology
1972US National Cancer Institute recommended creation of international registry of immunotherapy trials  Cancer immunotherapy, Oncology
1973First successful bone marrow transplant from unrelated donorGood, O'ReillyMemorial Sloan Kettering Cancer CenterCancer immunotherapy, Stem, cells, Transplantation, Oncology

May 1893

First successful treatment of cancer patient with immunotherapy

1895

Humans treated with antiserum prepared against human cancer. This established the principle of using serotherapy to fight cancer

1899

First commercial vaccine developed for treatment of sarcoma

1901 - 1903

First successful transplants of tumours in animals reported, providing a new experimental system for studying the role of the immune system in cancer

1902

First attempt to vaccinate against cancer with a patient's own tumour tissue

1908

Paul Ehrlich reports that spontaneously developed tumours can be suppressed by the immune system

1910

Austrian physicians Ernest Freund and Gisa Kaminer observed that something in blood serum from cancer patients pervents the destruction of cancer cells

1914

Experiments by James B Murphy demonstrate that lymphocytes help animals reject grafted tumours

1915

James B Murphy puts forward hypothesis that the nonspecific stimulation of lymphocytes could provide a cure for cancer based on experiments he and John J Morton carried out on mice

1916 - 1922

Disappointing results reported from clinical trials treating breast cancer patients with low doses of X-ray radiation following tumour removal, discrediting the theory that stimulation of lymphocytes could help cure cancer.

1924

Austrian physicians Ernest Freund and Gisa Kaminer discover a substance in intestines of cancer patients that reduce ability of normal serum to dissolve cancer cells.

1929

First molecular marker, antigen, identified on a tumour, laying foundation for use of antibodies to diagnose and treat cancer

Apr 1929

Autopsies carried out on tuberculosis patients show them less likely to have contracted cancer

1957 - 1959

Concept developed that the immune system naturally protects against cancer

25 Jul 1959

Mice injected with BCG vaccine shown to develop resistance to growth of implanted tumours. This was the first direct evidence of the immune system's ability to prevent cancer.

Dec 1966

Scientists detect antibodies to the Epstein-Barr virus in patients with nasopharyngeal cancer which suggest the cancer is caused by a virus.

Feb 1969

Team led by Karl and Ingegerd Hellstrom observe serum from mice with chemically induced tumours can block reaction of lymphocytes

Jun 1971

Hellstom team suggest that antibodies bound to tumour cells mask their detection by the immune system

1972

US National Cancer Institute recommended creation of international registry of immunotherapy trials

1973

First successful bone marrow transplant from unrelated donor