Year Event
1868 First report of an intentional infection of a cancer patient with erysipelas by Wilhelm Busch, with notable shrinkage of the tumor11
1883 Elie Metchnikoff publishes a key paper describing phagocytic cells(macrophages) in frogs102; awarded Nobel Prize in 1908
1890 Discovery of antibodies(diphtheria and tetanus) by Emil von Behring and Kitasato Shibasaburō103; Nobel Prize awarded to von Behring in 1901
1891 William Coley injected his first of many cancer patients with bacteria, reporting tumor regressions in many of them14
1895 Discovery of complement, by Jules Bordet104; awarded Nobel Prize 1919
1897-1901 Paul Ehrlich “Side-chain” theory of antibody specificity(adaptive immunity, autoimmunity)105; awarded Nobel Prize in 1908
1901 Serological discovery of blood groups, by Karl Landsteiner106; awarded Nobel Prize in 1930
1901-08 Rejection of transplanted tumors in mice, reported by Carl Jensen & Leo Loeb107,108
1914 Genetic basis for the rejection of transplantable tumors, reported by Clarence Little109
1909-20 Establishment of inbred strains of mice by Leonell Strong and Clarence Little110
1948 First report of histocompatibility antigens being the basis for transplant rejection, by P. Gorer, S. Lyman, & G. Snell111. 1908 Nobel Prize awarded jointly to G. Snell,B. Benacerraf, & J. Dausset in 1980
1955 Natural-Selection Theory of Antibody Formation, first formulated by N. Jerne112; awarded Nobel Prize in 1984
1956 Discovery of acquired immunological tolerance by R. Billingham, L. Brent & P.Medawar. Nobel Prize awarded to Medawar & F. Burnet in 1960113,114
1957 Immune rejection of transplanted syngeneic tumors(i.e., each tumor is antigenically unique)115. Reported by Richmond Prehn & Joan Main.
1957 Interferon discovered, described as a factor that conferred the property of viral interference116, reported by Alick Isaacs and Jean Lindenmann. Its anti-leukemic effect is reported in 1984.
1959 Immune surveillance of cancer theory by Lewis Thomas & F. Macfarlane Burnet3032
1959 Chemical structure of antibodies, by Gerald Edelmann & Rodney Porter117120; Nobel Prize awarded to both in 1972.
1959 BCG shown to have anti-tumor effects in a mouse model, reported by Lloyd Old, Donald Clark, & Baruj Benacerraf18
1973 First description of dendritic cells, by Ralph Steinman & Zanvil Cohn121; Steinman awarded Nobel Prize in 2011 for discovery of the dendritic cell and its role in adaptive immunity
1974 First reports of the specificity of cell-mediated immunity by Peter Doherty and Rolf Zinkernagel122,123; Nobel Prize awarded to both in 1996
1975 Monoclonal antibodies manufactured by George Koehler & Caesar Milstein124,125; Nobel Prize awarded to Koehler, Milstein & N. Jerne(for his theoretical contributions) in 1984
1975 Discovery of tumor necrosis factor, reported by Lloyd Old, with Elizabeth Carswell, Robert Kassel, S. Green, N. Fiore, & B. Williamson19
1975 First description of NK cells on a functional basis according to their ability to lyse tumor cells in the absence of prior stimulation126. Reported by Ronald Herberman, Myrthel Nunn, Howard Holden, & David H. Lavrin.
1976 Discovery of the genetic principle for generation of antibody diversity, by Susumu Tonegawa127,128; awarded Nobel Prize in 1987.
1982 Discovery of the T-cell receptor in 1982, reported by James Allison, B. McIntyre, & D. Bloch101
1984 First report of interferon response in patients with hairy cell leukemia129
1991 First report of a human tumor antigen recognized by T-cells, reported by Pierre van der Bruggen, C. Traversari, P. Chomez, et al.36
1996 Discovery that CTLA-4 blocking antibodies could treat tumors in animal models, reported by Dana Leach, Matthew Krummel & James Allison72
1998 Discoveries regarding the activation of innate immunity, by R. Medzhitov, P. Preston-Hurlburt, C. Janeway; & B. Beutler; Beutler awarded Nobel Prize in 2011130,131
2001 Rag2 -/-immunodeficient mice, with no B or T cells, show increased susceptibility to spontaneous and carcinogen-induced tumors, reported by V. Shankaran, with L.J. Old, R. Schreiber, et al.132
2005 Memory T-cells in colorectal tumors shown to predict clinical outcome, reported by F. Pagès, A. Berger, M. Camus et al.133
2010 First autologous cell-based cancer vaccine (sipuleucel-T) is approved by the FDA for the treatment of metastatic, asymptomatic stage IV prostate cancer43,134
2010 First successful use of gene-edited T-cells for the treatment of CD19+ hematologic malignancies in humans, reported by W. Qasim, H. Zhan, S. Samarasinghe et al.135
2011 Anti-CTLA-4(ipilimumab), is the first inhibitory checkpoint inhibitor(ICI) approved by the FDA for treatment of stage IV melanoma136
2012 Discovery of the CRISPR/Cas9 system, a simpler and more efficient method of genome editing, reported byJ.A. Doudna & E. Charpentier, with M. Jinek, K. Chylinski, I. Fonfara, & M. Hauer49
2013 First use of CRISPR/Cas9 technique in eukaryotic cells, reported by F. Zhang, with L. Cong, F. Ran, D. Cox, S. Lin, R. Barretto, N. Habib, P. Hsu, X. Wu, W. Jiang, & L. Marraffini50
2016 A second class of ICIs, anti-PD-1(pembrolizumab), is approved for the treatment of melanoma137
2016 First characterization of the role of dendritic cell CTLA-4 in Th-1 immunity, reported by M. Halpert, V.Konduri, D. Liang et al.138
2016 A third class of ICIs, PD-L1(atezolizumab), is approved for treatment of bladder cancer139
2016 First test in humans of CRISPR gene-editing technique for CAR T-cell therapy51
2017 Phase I/IIa study of an inhibitor of indoleamine 2,3-dioxygenase(IDO1), a non-membrane-attached enzyme with a checkpoint inhibitor function, shows promise95

cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead- Mohamed S. Aziz